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The purpose was to examine (1) the effect of measurement position and sex on femoral cartilage outcomes, and (2) the association between gait biomechanics and cartilage outcomes. Fifty individuals participated (25 males and 25 females; age = 20.62 [1.80] y). Ultrasound measured femoral cartilage thickness and echo-intensity at 90°, 115°, and 140° of knee flexion. Gait outcomes included the external knee adduction and knee flexion moments. Cartilage outcomes were compared using 2 (sex) × 3 (position) repeated-measures analysis of variance. Gait and cartilage associations were assessed using stepwise regression. Medial cartilage was thicker when measured at 90° compared with 115° (P =.02) and 140° (P <.01), and 115° compared with 140°, (P <.01) in males but not in females. Cartilage was thicker at 90° compared with 140° across both sexes within all regions (P <.01). Males had thicker cartilage than females in all positions (P <.01). Echo-intensity was lower at 90° than 115° (P <.01) and 140° (P =.01) in the central and lower at 90° than at 115° (P <.01) and 140° (P =.03) in lateral regions. No association was found between gait and cartilage outcomes. Ultrasound imaging position effects cartilage features more in males compared with females. Imaging position and sex influence cartilage outcomes and should be considered in study designs and clinical evaluation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Realignment osteotomy performed concomitantly with cartilage restoration typically requires early restricted weightbearing and can add significant morbidity, potentially leading to an increased risk of early perioperative complications. The purpose of this study was to compare the 30-day complication rates after isolated cartilage restoration (ICR) versus concomitant cartilage restoration and osteotomy (CRO) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. DESIGN: NSQIP registries between 2006 and 2019 were queried using Current Procedural Terminology codes to identify patients undergoing ICR (autologous chondrocyte implantation, osteochondral autograft transfer, or osteochondral allograft transplantation) and CRO (with concomitant high tibial osteotomy, distal femoral osteotomy, and/or tibial tubercle osteotomy). Complications rates between treatment groups were compared using multivariate logistic regression analyses adjusted for sex, age, steroid use, and respiratory status. RESULTS: A total of 773 ICR and 97 CRO surgical procedures were identified. Mean patient ages were 35.9 years for the ICR group and 31.2 years for the CRO group. Operative time was significantly longer in the CRO group (170.8 min) compared with the ICR group (97.8 min). Multivariate analysis demonstrated no significant differences in rates of PE, VTE, and all-cause readmission between the ICR and CRO groups. No events of wound disruption, SSI and reoperation were found in the CRO group, while the ICR group was characterized by low rates of wound disruption, reoperation, and SSI (

Objectives: To evaluate and characterise articular cartilage degeneration in patients with osteonecrosis of the femoral head (ONFH) using T2 mapping magnetic resonance imaging. Methods: We reviewed 35 patients with ONFH (20 males and 15 females, mean age: 45.7 ± 12.9 years) without obvious cartilage abnormalities on plain magnetic resonance imaging (ONFH group) and 25 healthy volunteers (9 males and 16 females, mean age: 42.9 ± 5.8 years) (control group). All patients underwent T2 mapping magnetic resonance imaging after ONFH onset. The region of interest was defined as the weight-bearing portion of the articular cartilage in the femoral head and acetabulum in the coronal view. Results: The T2 values of the articular cartilage of the acetabulum and femoral head, including necrotic and normal regions, were significantly higher in the ONFH group than those in the control group. These T2 values of the acetabulum and femoral head in Stages 3A and 2 were significantly higher in the ONFH group than those in the control group. Conclusions: The articular cartilage of the acetabulum and femoral head can deteriorate after the onset of ONFH, which may affect the natural history of ONFH and ONFH treatment. Our findings suggest the need for early intervention in joint preservation surgery. [ABSTRACT FROM AUTHOR]

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no‐go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8‐weeks post‐surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC‐microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight‐bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself. [ABSTRACT FROM AUTHOR]

Quantitative methods to characterize bone contusions and associated cartilage injury remain limited. We combined standardized voxelwise normalization and 3D mapping to automate bone contusion segmentation post‐anterior cruciate ligament (ACL) injury and evaluate anomalies in articular cartilage overlying bone contusions. Forty‐five patients (54% female, 26.4 ± 11.8 days post‐injury) with an ACL tear underwent 3T magnetic resonance imaging of their involved and uninvolved knees. A novel method for voxelwise normalization and 3D anatomical mapping was used to automate segmentation, labeling, and localization of bone contusions in the involved knee. The same mapping system was used to identify the associated articular cartilage overlying bone lesions. Mean regional T1ρ was extracted from articular cartilage regions in both the involved and uninvolved knees for quantitative paired analysis against ipsilateral cartilage within the same compartment outside of the localized bone contusion. At least one bone contusion lesion was detected in the involved knee within the femur and/or tibia following ACL injury in 42 participants. Elevated T1ρ (p = 0.033) signal were documented within the articular cartilage overlying the bone contusions resulting from ACL injury. In contrast, the same cartilaginous regions deprojected onto the uninvolved knees showed no ipsilateral differences (p = 0.795). Automated bone contusion segmentation using standardized voxelwise normalization and 3D mapping deprojection identified altered cartilage overlying bone contusions in the setting of knee ACL injury. [ABSTRACT FROM AUTHOR]

Intra‐articular corticosteroid injections, such as triamcinolone acetonide (TA), are commonly used by clinicians to manage joint synovial inflammation. However, due to conflicting evidence in literature, there is a fear among clinicians that the injections may be harmful to otherwise healthy cartilage in young patients. The purpose of this study was to evaluate the effects of TA on young, healthy chondrocytes. Articular cartilage samples were harvested from bovine knee joints (1–2 months old). In both healthy and inflammatory (interleukin‐1β) challenged cartilage, samples were treated with TA at doses ranging from 1 nM to 200 μM. Following a short‐ (2 days) or long‐term (10–14 days) treatment, chondrocyte viability, proliferation, and extracellular matrix (ECM) synthesis and degradation were evaluated with a click chemistry‐based technique. Chondrocyte viability, proliferation, and anabolic activity were all minimally affected by short‐term and long‐term TA treatment. After both acute and sustained inflammatory challenges, TA reduced the catabolic activities in cartilage, reducing nascent glycosaminoglycan loss and maintaining cartilage mechanical properties. Overall, at physiologically relevant doses, TA had minimal negative impact on chondrocytes when maintained within their native ECM. Clinical significance: The findings provide new insight for current clinical practices concerning the use of TA in intra‐articular injections, especially in young patients, and established a foundation for future investigations into the impact of corticosteroids on joint homeostasis. [ABSTRACT FROM AUTHOR]

Background: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. Objective: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). Methods: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin‐1β (rrIL‐1β) and SDC4 small interfering RNA (si‐SDC4). Anti‐SDC4 ectodomain‐specific antibodies or IgG were intra‐articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4‐cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col‐II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. Results: SDC4 expression was evidently increased in MIA‐model animals compared to control groups. rrIL‐1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col‐II. These effects were reversed by si‐SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col‐II and ACAN, and a decrease in SDC4, MMP13 and cleaved‐CASP3‐positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. Conclusions: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA. [ABSTRACT FROM AUTHOR]

Early diagnosis of post‐traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high‐resolution imaging to investigate early‐stage deterioration in articular cartilage and the subchondral bone plate from a sub‐critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2‐ and 14‐week post‐impact surgery, cartilage‐bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (μCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post‐impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post‐impact, only minor, non‐significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2‐week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries. [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential for accelerating continuous‐wave (CW) T1ρ dispersion measurement with compressed sensing approach via studying the effect that the data reduction has on the ability to detect differences between intact and degenerated articular cartilage with different spin‐lock amplitudes and to assess quantitative bias due to acceleration. Methods: Osteochondral plugs (n = 27, 4 mm diameter) from femur (n = 14) and tibia (n = 13) regions from human cadaver knee joints were obtained from commercial biobank (Science Care, USA) under Ethical permission 134/2015. MRI of specimens was performed at 9.4T with magnetization prepared radial balanced SSFP (bSSFP) readout sequence, and the CWT1ρ relaxation time maps were computed from the measured data. The relaxation time maps were evaluated in the cartilage zones for different acceleration factors. For reference, Osteoarthritis Research Society International (OARSI) grading and biomechanical measurements were performed and correlated with the MRI findings. Results: Four‐fold acceleration of CWT1ρ dispersion measurement by compressed sensing approach was feasible without meaningful loss in the sensitivity to osteoarthritic (OA) changes within the articular cartilage. Differences were significant between intact and OA groups in the superficial and transitional zones, and CWT1ρ correlated moderately with the reference measurements (0.3 < r < 0.7). Conclusion: CWT1ρ was able to differentiate between intact and OA cartilage even with four‐fold acceleration. This indicates that acceleration of CWT1ρ dispersion measurement by compressed sensing approach is feasible with negligible loss in the sensitivity to osteoarthritic changes in articular cartilage. [ABSTRACT FROM AUTHOR]

BACKGROUND: The traditional view is that proximal fibular fractures do not require fixation. Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint, and its mechanism of action is worth studying. OBJECTIVE: To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS: Finite element method was used to conduct simulated biomechanical experiments. A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data, and four proximal fibular shapes were simulated (Model A: intact, Model B: 1 cm fracture below the fibular head, Model C: 1 cm tip defect fracture from the proximal end of the fibula to the distal end, and Model D: 2 cm bone defect from the proximal end of the fibula). A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION: (1) In Model A, the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment, while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment. The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle, and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle. (2) Compared to Model A, there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C. (3) Compared to Model A, the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage (14.9%), medial condyle of femoral cartilage (13.6%), and medial meniscus (6.6%). The maximum first principal stress increase amplitude was the medial meniscus (11.06%), the medial tibial cartilage (8.65%), and the medial condyle of the femoral cartilage (7.46%). The maximum equivalent stress increase amplitude of the ligament was as follows: popliteal arch ligament (33.2%)>anterior cruciate ligament (21.3%)>fibular collateral ligament (17%)>posterior cruciate ligament (14.3%)>anterior lateral collateral ligament (13.2%)>medial collateral ligament (10.1%). (4) Compared to Model A, the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage (19.5%), femoral cartilage medial condyle (17.9%), and medial meniscus (9.9%). The maximum first principal stress in sequence was the medial meniscus (14.04%), the medial tibial cartilage (13.03%), and the medial condyle of the femoral cartilage (11.37%). The increasing trend of maximum equivalent stress in ligaments was as follows: anterior cruciate ligament (25.2%)>posterior cruciate ligament (18.9%)>medial collateral ligament (18.5%)>anterior lateral collateral ligament (12.7%). (5) It is suggested that when the knee joint is extended, a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage, anterior cruciate ligament, and posterior lateral ligament complex. [ABSTRACT FROM AUTHOR]

Hydrogels have emerged as promising candidates for biomedical applications, such as replacing natural articular cartilage, owing to their unique viscoelastic properties. However, sufficient mechanical properties, self‐healing ability, and adhesive nature are some issues limiting its application window. Here, a facile one‐pot synthesis of dual cross‐linked zinc‐coordinated copolymer hydrogels is presented. The network structure of the copolymer hydrogels is strategically developed via dynamic and reversible physical cross‐linking by Zn2+ ions and simultaneous covalent cross‐linking through a covalent cross‐linker viz methylene bisacrylamide. Fourier‐transform infrared (FTIR), X‐ray diffraction (XRD) scanning electron microscopy (SEM), and Brunauer–Emmett–Teller (BET) analysis have thoroughly characterized the structure of the synthesized hydrogels. The introduction of Zn2+ offers dynamic and reversible complexation, leading to excellent mechanical properties and self‐healing features. Moreover, the percentage of the equilibrium water content of zinc‐coordinated copolymer hydrogel samples is comparable with that of natural articular cartilage. The Shear sliding study shows the dominant adhesive behavior of HGel‐Zn(NO3)2 sample compared to the parent HGel sample. This facile dual cross‐linked hydrogel, HGel‐Zn(NO3)2, with a combination of good mechanical properties, efficient self‐recovery, adequate water content, and favorable adhesive nature, seems very promising to mimic the articular cartilage. [ABSTRACT FROM AUTHOR]

Diseased conditions of articular cartilage such as osteoarthritis (OA) are accompanied by a change in the water concentration, together with a decrease in cartilage thickness. These parameters are important indicators of the normal joint functioning. Light scattering in a heterogeneous joint tissue is a complex process and it is important to supplement its study with understanding gained from modelling. In this work we employed Monte Carlo for analysis of the relationship between changes in cartilage parameters and calculated diffuse reflectance spectra. It has been shown that water absorption peak at 980 nm is determined by both water content and cartilage thickness, while changes in diffuse reflectance spectra at 1450 nm are mostly driven only by water content. Since independent assessment of these parameters is clinically relevant, several approaches for their determination were developed. A heuristic algorithm for cartilage thickness determination and its quality metrics (R 2 = 0.96) were obtained. Several regression models were developed using the amplitudes of diffuse reflectance spectra at different wavelengths and it was shown that the use of a wide range of wavelengths (850–1700 nm) allows to determine the cartilage water concentration and its thickness with the accuracy R 2 0.96 and 0.99 while measuring at different probe-detector distances. [ABSTRACT FROM AUTHOR]

Chondrocytes, the resident cells of articular cartilage, play a vital role in tissue maintenance and regeneration. Recent studies have highlighted chondrocyte senescence as a key contributor to cartilage dysfunction. In this study, we investigated the influence of substrate stiffness on chondrocyte senescence using polydimethylsiloxane (PDMS) substrates with varying stiffness ratios (1:5, 1:20, and 1:60). After culturing chondrocytes on these substrates, we found that softer substrates (1:60) significantly reduced chondrocyte senescence, as evidenced by a decrease in senescence‐associated β‐galactosidase (SA‐β‐gal) activity by 33% compared with stiffer substrates (1:5). Furthermore, quantitative real‐time polymerase chain reaction (PCR) analysis revealed that chondrocytes cultured on softer substrates exhibited lower expression levels of senescence‐related genes (e.g., p16INK4a) and matrix‐degrading enzymes (e.g., MMP13). These findings suggest that substrate stiffness plays a critical role in regulating chondrocyte senescence and could potentially inform the design of scaffolds for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Lack of insight into factors that determine purity and quality of human iPSC (hiPSC)-derived neo-cartilage precludes applications of this powerful technology toward regenerative solutions in the clinical setting. Here, we set out to generate methylome-wide landscapes of hiPSC-derived neo-cartilages from different tissues-of-origin and integrated transcriptome-wide data to identify dissimilarities in set points of methylation with associated transcription and the respective pathways in which these genes act. Methods: We applied in vitro chondrogenesis using hiPSCs generated from two different tissue sources: skin fibroblasts and articular cartilage. Upon differentiation toward chondrocytes, these are referred to as hFiCs and hCiC, respectively. Genome-wide DNA methylation and RNA sequencing datasets were generated of the hiPSC-derived neo-cartilages, and the epigenetically regulated transcriptome was compared to that of neo-cartilage deposited by human primary articular cartilage (hPAC). Results: Methylome-wide landscapes of neo-cartilages of hiPSCs reprogrammed from two different somatic tissues were 85% similar to that of hPACs. By integration of transcriptome-wide data, differences in transcriptionally active CpGs between hCiC relative to hPAC were prioritized. Among the CpG-gene pairs lower expressed in hCiCs relative to hPACs, we identified genes such as MGP, GDF5, and CHAD enriched in closely related pathways and involved in cartilage development that likely mark phenotypic differences in chondrocyte states. Vice versa, among the CpG-gene pairs higher expressed, we identified genes such as KIF1A or NKX2-2 enriched in neurogenic pathways and likely reflecting off target differentiation. Conclusions: We did not find significant variation between the neo-cartilages derived from hiPSCs of different tissue sources, suggesting that application of a robust differentiation protocol such as we applied here is more important as compared to the epigenetic memory of the cells of origin. Results of our study could be further exploited to improve quality, purity, and maturity of hiPSC-derived neo-cartilage matrix, ultimately to realize introduction of sustainable, hiPSC-derived neo-cartilage implantation into clinical practice. [ABSTRACT FROM AUTHOR]

A new concept of biomimetic lubricating nanosystem that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property is developed. High drug loading ratio of 99%, great friction reduction by 75% for more than 7200 times without failure, and effective up-regulation of cartilage anabolic genes and down-regulation of catabolic proteases and pain-related genes are achieved. Our work provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for synergistic therapy of osteoarthritis. [Display omitted] Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core–shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications. [ABSTRACT FROM AUTHOR]

There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra‐articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra‐articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6‐month‐old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center‐edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real‐time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C‐KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI. [ABSTRACT FROM AUTHOR]

Articular cartilage injuries in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. While there is a vast amount of research into cartilage regeneration, integrating engineered implants with cartilage remains a challenge. As cartilage is a load bearing tissue, it is imperative to evaluate tissue repair strategies and their ability to integrate under mechanical loading. This work established a dynamically loaded ex vivo model of cartilage repair using human cartilage explants. The model was used to assess the efficacy of a stem cell therapy delivered in a bioadhesive hydrogel comprised of photocrosslinkable gelatin methacryloyl (GelMA) and microbial transglutaminase to repair the model defect. Extensive neocartilage production and integration were observed via histology and immunohistochemistry after 28 days chondrogenic culture. Analysis of culture media allowed monitoring of glycosaminoglycan and type II collagen production over time. A mechanical assessment of integration via a push out test showed a 15-fold increase in push out strength over the culture duration. The model was successful in exhibiting robust chondrogenesis with transglutaminase or without, and under both culture conditions. The work also highlights several limitations of ex vivo models and challenges of working with bioreactors that must be overcome to increase their utility. This ex vivo model has the potential to delay the need for costly pre-clinical studies and provide a more nuanced assessment of cartilage repair strategies than is possible in vivo. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a degenerative disease of synovial joints affecting all tissues, including articular cartilage and subchondral bone. Osteoarthritis animal models can recapitulate aspects of human disease progression and are used to test efficacy of drugs, biomaterials, and cell therapies. The rat medial meniscus transection (MMT) model is a surgically induced posttraumatic osteoarthritis model commonly used for preclinical therapeutic screening. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes at early‐, mid‐, and late‐stages of osteoarthritis progression. Tibia of MMT‐operated animals showed proteoglycan loss and fibrillation along articular cartilage surfaces as early as 3‐weeks post‐surgery. With contrast‐enhanced micro‐CT technique, quantitative, 3‐dimensional analysis of the tibia showed that the articular cartilage thickened at 3‐ and 6‐weeks post‐surgery and decreased at 12‐weeks post‐surgery. This decreased cartilage thickness corresponded with increased lesions in the articular cartilage that led to its full degradation and exposing the subchondral bone layer. Further, subchondral bone thickening was significant at 6‐weeks post‐surgery and followed cartilage damage. Osteophytes were found as early as 3‐weeks post‐surgery and coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization, suggesting endochondral ossification. The rat MMT model has predominantly been used out to 3‐weeks, and most studies determined the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6‐ and 12‐weeks more resembled severe phenotypes of human osteoarthritis. Thus, evaluating novel therapeutics at late‐stage will be important for eventual clinical translation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found an association between basal metabolic rate (BMR) and various malignant neoplasms, including bone tumors. BMR is also associated with bone mineral density, but the causality between BMR and benign neoplasms of bone and articular cartilage remains uncertain. Design: Single nucleotide polymorphisms (SNPs) associated with BMR (p < 5 × 10-8) were used as instrumental variables for Mendelian randomization analysis of neoplasm risk. The inverse variance weighted (IVW) method was the primary approach, with the weighted median and MR-Egger regression serving as supplements. Results: In this MR analysis, the IVW method supported a causal relationship between BMR and benign neoplasms of bone and articular cartilage (OR = 1.417; 95% CI, 1.039 to 1.930; p = 0.027). No evidence of heterogeneity or pleiotropy in the selected SNPs was found in our study. Thus, based on these results, we discovered a possible causal relationship between BMR and benign neoplasms of bone and articular cartilage. Conclusions: In this MR study, evidence suggested a genetic correlation between genetically predicted BMR and the risk of neoplasms in bone and articular cartilage. [ABSTRACT FROM AUTHOR]

Aims: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by pain and functional limitations. Current treatments offer symptomatic relief but do not address the underlying pathology. This study explores the role of the infrapatellar fat pad (IFP) in KOA and evaluates the efficacy of its partial arthroscopic excision. Methods: A retrospective review was conducted on 37 KOA patients who underwent partial IFP excision. Pain and function were assessed using the WOMAC and VAS scores, while MRI evaluations focused on cartilage health. Results: Significant postoperative improvements were observed in both pain and functional outcomes, with substantial reductions in WOMAC and VAS scores (P < 0.001). MRI findings demonstrated notable enhancements in cartilage integrity, reflected in significantly improved WORMS scores (P < 0.001). Conclusions: Partial excision of the IFP significantly reduces pain and improves function in KOA patients, while also promoting cartilage health. These findings support the IFP's role in KOA pathology and highlight the potential benefits of targeted surgical intervention. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence Chondral and osteochondral lesions in the knee are common conditions that significantly impair individuals' well‐being and can lead to osteoarthritis, imposing substantial burdens on healthcare systems. The limited natural healing capacity of articular cartilage necessitates innovative treatment strategies. Microfracture (MF) is a widely used technique for knee chondral defects, but its long‐term efficacy is often inadequate. Although recent randomised controlled trials have compared microfractures with scaffold‐enhanced therapies, a comprehensive systematic review and meta‐analysis are lacking.An extensive literature search was conducted in PubMed and EMBASE databases following PRISMA guidelines. Inclusion criteria focused on randomised controlled trials (RCTs) comparing microfractures alone to matrix‐induced chondrogenesis for knee chondral defects with at least a 12‐month follow‐up. Ten randomised controlled trials conducted between 2013 and 2024, enroling 378 patients, were included.The meta‐analysis showed no significant superiority of scaffolds over MF (p > 0.05) in International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome, Visual Analog Scale, and Magnetic Resonance Observation of Cartilage Repair Tissue scores at 12 and 24 months. However, individual studies suggested the potential benefits of scaffolds, especially in long‐term outcomes. Clinical improvements from MF typically decline after 2–3 years, underscoring the need for long‐term follow‐up in future research.Our meta‐analysis shows no significant difference between MF and MF with scaffold in treating knee cartilage defects, though some long‐term RCTs demonstrate statistically significant differences. The absence of a universally accepted algorithm for analysing knee chondral defects limits this study. Establishing reliable guidelines and standardised study protocols is essential to improve long‐term patient outcomes and the quality of future papers.Level I [ABSTRACT FROM AUTHOR]

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits. Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA. Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR. Conclusions: CGMR might improve cartilage regeneration in osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: Oxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs. Methods: The predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations. Results: There were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007). Conclusions: An intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA. [ABSTRACT FROM AUTHOR]

In articular cartilage, the pericellular matrix acting as a specialized mechanical microenvironment modulates environmental signals to chondrocytes through mechanotransduction. Matrix viscoelastic alterations during cartilage development and osteoarthritis (OA) degeneration play an important role in regulating chondrocyte fate and cartilage matrix homeostasis. In recent years, scientists are gradually realizing the importance of matrix viscoelasticity in regulating chondrocyte function and phenotype. Notably, this is an emerging field, and this review summarizes the existing literatures to the best of our knowledge. This review provides an overview of the viscoelastic properties of hydrogels and the role of matrix viscoelasticity in directing chondrocyte behavior. In this review, we elaborated the mechanotransuction mechanisms by which cells sense and respond to the viscoelastic environment and also discussed the underlying signaling pathways. Moreover, emerging insights into the role of matrix viscoelasticity in regulating chondrocyte function and cartilage formation shed light into designing cell‐instructive biomaterial. We also describe the potential use of viscoelastic biomaterials in cartilage tissue engineering and regenerative medicine. Future perspectives on mechanobiological comprehension of the viscoelastic behaviors involved in tissue homeostasis, cellular responses, and biomaterial design are highlighted. Finally, this review also highlights recent strategies utilizing viscoelastic hydrogels for designing cartilage‐on‐a‐chip. Summary: It is well known that viscoelasticity has been found to be a universal characteristic of living tissues, cells, and molecules.Matrix viscoelasticity, as a critical physical cues of cartilage matrix microenvironment, regulates collective chondrocyte fate and cartilage formation. But, how matrix viscoelasticity affects the chondrocyte behavior and function remains unclear.Growing evidence has demonstrated that matrix viscoelasticity regulates chondrocytes in some ways not anticipated from previous mechanisms of mechanotransduction, which was based on purely substrate stiffness.In this review, we introduce recent work elucidating the effect of matrix viscoelasticity on chondrocytes morphology, phenotype, function, inflammatory response, and signaling pathways.These findings have provided insights into viscoelasticity as a design parameter for cartilage tissue engineering, regenerative medicine, and cartilage‐on‐a‐chip, even shed light into the pathological mechanism of joint growth and degeneration. [ABSTRACT FROM AUTHOR]

Purpose: Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long‐term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. Methods: Matrix‐assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale, and Tegner scores at 14‐year mean follow‐up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patient and/or the selection of a match‐paired subgroup to compare homogeneous men and women patients. Results: At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow‐ups (at 14 years: 77.2 ± 18.9 vs. 62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match‐paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: −1.6 ± 1.7 vs. −1.9 ± 1.6). Conclusion: Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long‐term results. When both sexes are compared with homogeneous match‐paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long‐term outcome after MACT. Level of Evidence: Level II. [ABSTRACT FROM AUTHOR]

Background: Osteochondral defects of the medial femoral condyle combined with varus malalignment in young and active patients are a debilitating condition, which can result in early osteoarthritis. Osteochondral autologous transfer (OAT) combined with valgus high tibial osteotomy (HTO) might therefore be a comprehensive solution to maintain long-term knee function. Purpose/Hypothesis: The purpose of this study was to report clinical results and survivorship after combined OAT and valgus HTO for symptomatic osteochondral defects of the medial femoral condyle in the setting of varus malalignment at a long-term follow-up. It was hypothesized that undergoing combined OAT and valgus HTO would produce favorable clinical results along with a low rate of conversion to arthroplasty. Study Design: Case series; Level of evidence, 4. Methods: All patients treated between 1998 and 2008 with combined valgus HTO and OAT for deep osteochondral defects of the medial femoral condyle and concomitant varus malalignment >2° without meniscal repair/transplantation, osteoarthritis, or ligamentous instability/reconstruction were included. The survival rates of this combined procedure were evaluated. Failure was defined as conversion to knee joint arthroplasty during the follow-up period. Patient-reported outcomes were collected pre- and postoperatively, including the Lysholm score, visual analog scale score, Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale score, and subjective level of satisfaction (scale 0-10). Results: Of 74 patients who were included for 10-year follow-up, 3 had died. A total of 15 patients were lost to follow-up, so 56 patients could be reevaluated, for a follow-up rate of nearly 80%. The mean age at surgery was 38.8 ± 9.9 years (range, 19.9-62.4 years), and the mean follow-up time was 18.9 ± 3.0 years (median, 18.8 years; range, 14.1-24.8 years). The survival rates were 87% at 10 years, 86% at 15 years, and 77% at 19 years after surgery. At final follow-up, the Lysholm score showed a mean increase of 39 points (95% CI, 25.4-50.0 points; P <.001) from 40 points to 79 points, representing a significant improvement. Overall, 96% of patients surpassed the minimal clinically important difference (MCID) for the Lysholm score. The visual analog scale score decreased by a mean of 4.8 points (range, 5-10 points) from 7.5 points to 2.7 points (P <.001), and 80% of patients surpassed the MCID. The mean Tegner Activity Scale score was 4.5 ± 1.6, and the mean KOOS subscale scores at final follow-up were as follows: Pain: 81 ± 21 (range, 19-100), Symptoms: 80 ± 22 (range, 21-100), Activities of Daily Living: 85 ± 21 (range, 18-100), Sports: 68 ± 32 (range, 0-100), and Quality of Life: 67 ± 28 (range, 0-100). Overall, 78% of the patients were satisfied with the results of the operation. Conclusion: The combination of OAT and valgus HTO presents a viable treatment option for patients affected by osteochondral defects of the medial femoral condyle and concurrent varus malalignment. A sustained and substantial improvement in clinical outcomes, significantly reduced pain severity, and a high rate of long-term survivorship can be anticipated in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Many adolescents experience knee pain, and only some undergo detailed imaging. In this population, the prevalence of abnormalities and normal variants on magnetic resonance imaging (MRI) scans is unknown. Purpose: To investigate the prevalence of abnormalities and normal variants of the knee on MRI scans and their relationship with participant characteristics in the general young adolescent population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study was part of an open population-based cohort study that focuses on health, growth, and development from fetal life until adulthood. Between 2017 and 2020, adolescents aged 12 to 15 years underwent MRI of both knees. These MRI scans were assessed in a standardized way for abnormalities and normal variants to determine their prevalence. Logistic regression was used to analyze the presence of abnormalities and normal variants in relation to sex, height, weight, body mass index–standard deviation (BMI-SD), and ethnicity. Results: A total of 1910 participants (median age, 13.5 years; interquartile range, 13.4-13.7 years; 52% girls) were included in this study. Of them, 370 (19.4%) participants had at least 1 abnormality or normal variant. Bone marrow edema around the knee was the most prevalent finding, affecting 140 (7.3%) participants. In 107 (5.6%) participants, nonossifying fibromas were found. A total of 43 (2.3%) participants had characteristics of Osgood-Schlatter disease, 16 (0.8%) showed characteristics of Sinding-Larsen-Johansson syndrome, and osteochondritis dissecans was found in 13 (0.7%) participants. Variants such as discoid menisci were found in 40 (2.1%) participants and a bipartite patella in 21 (1.1%) participants. There were multiple associations between abnormalities or variants and participant characteristics, including bone marrow edema being more often present in boys (odds ratio [OR], 2.44; 95% CI, 1.69-3.52) and those with a lower BMI-SD (OR, 0.85; 95% CI, 0.73-0.98). Osgood-Schlatter and osteochondritis dissecans were more often present in boys (OR, 4.21 [95% CI, 2.01-8.85] and OR, 13.18 [95% CI, 1.71-101.58], respectively). Discoid menisci were associated with a non-Western ethnicity (OR, 2.06; 95% CI, 1.07-3.96) and higher BMI-SD (OR, 2.34; 95% CI, 1.76-3.11). Conclusion: Abnormalities and normal variants on MRI scans of the knees are common in adolescents. Physicians who are involved in the treatment of adolescents with knee pain need to be aware of this prevalence so that these children will not be overtreated or misdiagnosed. [ABSTRACT FROM AUTHOR]

Background: Despite being recognized as a safe procedure with minimal reported complications, injecting autologous bone marrow aspirate concentrate (BMAC) as an adjuvant to arthroscopic partial meniscectomy (APM) for symptomatic patients with meniscal tears and concomitant knee osteoarthritis (OA) has not been studied in randomized controlled trials. Purpose: To compare patient-reported outcome measure (PROM) scores and radiographic outcomes in symptomatic patients with meniscal tears and concomitant mild knee OA who underwent APM with and without an autologous BMAC injection administered at the time of surgery. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Enrolled patients aged ≥18 years determined to have a symptomatic meniscal tear with concomitant mild knee OA suitable for APM and meeting inclusion and exclusion criteria were randomized into 2 groups: BMAC and control (no BMAC). The primary endpoint of the study was the International Knee Documentation Committee (IKDC) score at 1 year postoperatively. Secondary endpoints included radiographic outcomes (Kellgren-Lawrence grade) at 1 year postoperatively and various PROM scores, including those for the IKDC, Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale, and Veterans RAND 12-Item Health Survey, at 3 months, 6 months, 1 year, and 2 years after meniscectomy. Results: Of the 95 enrolled patients, 83 (87.4%) were included for final analysis. No significant differences were found between the groups with regard to patient characteristics, intraoperative variables, concomitant procedures, preoperative PROM scores, or preoperative radiographic findings. At 1 year postoperatively, the BMAC group failed to demonstrate significantly better IKDC scores (P =.687) or radiographic outcomes (P >.05 for all radiographic measures) compared with the control group. Secondary PROM scores also did not significantly differ between the groups (P >.05 for all PROMs). However, there were higher achievement rates of the minimal clinically important difference for the KOOS Sport (100.0% vs 80.0%, respectively; P =.023) and KOOS Symptoms (92.3% vs 68.0%, respectively; P =.038) at 1 year postoperatively in the BMAC group than in the control group. All PROMs, excluding the VR-12 mental score, showed significant improvements compared with baseline at all postoperative time points for both the BMAC and control groups. Conclusion: The addition of an autologous BMAC injection during APM did not result in significant changes in IKDC scores or radiographic outcomes at the 1-year postoperative mark. Secondary PROM scores were generally comparable between the 2 groups, but there was higher minimal clinically important difference achievement for the KOOS Sport and KOOS Symptoms at 1 year postoperatively in the BMAC group. In patients with symptoms consistent with a meniscal tear who had concomitant mild OA, the addition of BMAC to arthroscopic debridement did not affect the outcome. Registration: NCT02582489 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Cationic contrast‐enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in vivo imaging at clinical resolution. We hypothesize that repeated administration of CA4+ will have no adverse side effects or complications, and that sequential in vivo imaging assessments will distinguish articular cartilage repair tissue from early degenerative and healthy cartilage in critically sized chondral defects. In an established equine translational preclinical model, lameness and synovial effusion scores are similar to controls after repeated injections of CA4+ (eight injections over 16 weeks) compared to controls. Synovial fluid total protein, leukocyte concentration, and sGAG and PGE2 concentrations and articular cartilage and synovial membrane scores are also equivalent to controls. Longitudinal in vivo cationic CECT attenuation in repair tissue is significantly lower than peripheral to (adjacent) and distantly from defects (remote sites) by 4 weeks (p < 0.001), and this difference persists until 16 weeks. At the 6‐ and 8‐week time points, the adjacent locations exhibit significantly lower cationic CECT attenuation compared with the remote sites, reflecting peri‐defect degeneration (p < 0.01). Cationic CECT attenuation at clinical resolution significantly correlates with cationic CECT (microCT) (r = 0.69, p < 0.0001), sGAG (r = 0.48, p < 0.0001), and ICRS II histology score (r = 0.63, p < 0.0001). In vivo cationic CECT imaging at clinical resolution distinguishes fibrous repair tissue from degenerative and healthy hyaline cartilage and correlates with molecular tissue properties of articular cartilage. [ABSTRACT FROM AUTHOR]

MXenes nanosheets with high conductivity, hydrophilicity, and excellent reactive oxygen species (ROS) scavenging ability have shown promise in treating various degenerative diseases correlated with abnormal ROS accumulation. Herein, the therapeutic potential of Ti3C2Tx nanosheets, which is the most widely investigated MXene material, in delaying osteoarthritis (OA) progression is demonstrated. In vitro experiments indicate the strong ROS scavenging capacity of Ti3C2Tx nanosheets and their acceptable biocompatibility. Ti3C2Tx nanosheets effectively protect chondrocytes from cell death induced by oxidative stress. In addition, Ti3C2Tx nanosheets demonstrate a prominent anti-inflammatory effect and the ability to restore homeostasis between anabolic activities and catabolic activities in chondrocytes. Furthermore, RNA sequencing reveals the potential mechanism underlying the Ti3C2Tx nanosheet-mediated therapeutic effect. Finally, the in vivo curative effect of Ti3C2Tx nanosheets is verified using a rat OA model. Histological staining and immunohistochemical analyses indicate that Ti3C2Tx nanosheets effectively ameliorate OA progression. Conclusively, the in vitro and in vivo experiments suggest that Ti3C2Tx nanosheets could be a promising and effective option for OA treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: We previously reported that traction magnetic resonance imaging (MRI) of the elbow without arthrography increases the width of the radiocapitellar joint (RC) and improves articular cartilage visibility. However, the effects of axial traction on different age groups have not yet been evaluated. We hypothesized that the effect of traction would decrease as the participants' age increased. Methods: We enrolled 30 healthy volunteers, ten each in their 20s, 30s, and 40s. The male-to-female ratio in each age group was 1:1. Elbow MRI was performed without traction and with 3, 5, and 7 kg axial traction. We evaluated joint space width (JW), humeral articular cartilage visibility, and intraprocedural pain/discomfort. We measured JW and cartilage visibility at the RC and the lateral and medial thirds of the ulnohumeral joint. Results: The older age groups exhibited narrower JWs without traction. Axial traction increased the JW and improved the visibility of the RC in all age groups. No significant differences were observed in the ulnohumeral joint's lateral or medial thirds, but pain and discomfort increased with heavier traction weights. Conclusions: For participants in their 20s and 30s, axial traction of 3 kg seemed appropriate, while 7 kg traction was considered for those in their 40s. [ABSTRACT FROM AUTHOR]

Treatment of articular cartilage remains a great challenge due to its limited self-repair capability. In tissue engineering, a scaffold with both mechanical strength and regenerative capacity has been highly desired. This study developed a double-network scaffold based on natural biomaterials of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) using three-dimensional (3D) printing technology. Structural and mechanical characteristics of the scaffold was first investigated. To enhance its ability of recruiting endogenous bone marrow mesenchymal stem cells (BMSCs), the scaffold was conjugated with a proven BMSC-specific-affinity peptide E7, and its biocompatibility and capacity of cell recruitment were assessed in vitro. Animal experiments were conducted to evaluate cartilage regeneration after transplantation of the described scaffolds. The SF/HA scaffolds exhibited a hierarchical macro-microporous structure with ideal mechanical properties, and offered a 3D spatial microenvironment for cell migration and proliferation. In vitro experiments demonstrated excellent biocompatibility of the scaffolds to support BMSCs proliferation, differentiation, and extracellular matrix production. In vivo, superior capacity of cartilage regeneration was displayed by the SF/MAHA + E7 scaffold as compared with microfracture and unconjugated SF/MAHA scaffold based on macroscopic, histologic and imaging evaluation. In conclusion, this structurally and functionally optimized SF/MAHA + E7 scaffold may provide a promising approach to repair articular cartilage lesions in situ. [ABSTRACT FROM AUTHOR]

Articular cartilage degeneration poses a significant public health challenge; techniques such as 3D bioprinting are being explored for its regeneration in vitro. Gelatin-based hydrogels represent one of the most promising biopolymers used in cartilage tissue engineering, especially for its collagen composition and tunable mechanical properties. However, there are no standard protocols that define process parameters such as the crosslinking method to apply. To this aim, a reproducible study was conducted for exploring the influence of different crosslinking methods on 3D bioprinted gelatin structures. This study assessed mechanical properties and cell viability in relation to various crosslinking techniques, revealing promising results particularly for dual (photo + ionic) crosslinking methods, which achieved high cell viability and tunable stiffness. These findings offer new insights into the effects of crosslinking methods on 3D bioprinted gelatin for cartilage applications. For example, ionic and photo-crosslinking methods provide softer materials, with photo-crosslinking supporting cell stretching and diffusion, while ionic crosslinking preserves a spherical stem cell morphology. On the other hand, dual crosslinking provides a stiffer, optimized solution for creating stable cartilage-like constructs. The results of this study offer a new perspective on the standardization of gelatin for cartilage bioprinting, bridging the gap between research and clinical applications. [ABSTRACT FROM AUTHOR]

AbstractDamage to articular cartilage is irreversible and its ability to heal is minimal. The development of articular cartilage in tissue engineering requires suitable biomaterials as scaffolds that provide a 3D natural microenvironment for the development and growth of articular cartilage. This study aims to investigate the applicability of a 3D printed CSH (collagen type II/silk fibroin/hyaluronic acid) scaffold for constructing cartilage tissue engineering. The results showed that the composite scaffold had a three-dimensional porous network structure with uniform pore sizes and good connectivity. The hydrophilicity of the composite scaffold was 1071.7 ± 131.6%, the porosity was 85.12 ± 1.6%, and the compressive elastic modulus was 36.54 ± 2.28 kPa. The creep and stress relaxation constitutive models were also established, which could well describe the visco-elastic mechanical behavior of the scaffold. The biocompatibility experiments showed that the CSH scaffold was very suitable for the adhesion and proliferation of chondrocytes. Under dynamic compressive loading conditions, it was able to promote cell adhesion and proliferation on the scaffold surface. The 3D printed CSH scaffold is expected to be ideal for promoting articular cartilage regeneration. [ABSTRACT FROM AUTHOR]

Objectives: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR‐21‐5p may participate in the TMJOA development and the interaction between circRNA‐ACAP2 (CircACAP2) and miR‐21‐5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. Materials and Methods: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR‐21‐5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual‐luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. Results: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR‐21‐5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. Conclusions: The present study unveiled that CircACAP2/miR‐21‐5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA. [ABSTRACT FROM AUTHOR]

Objective: Cartilage and meniscus are important structures that maintain the health of the knee joint. Early detection of changes in the internal components of cartilage and meniscus before morphological changes occur is essential to prevent and delay the development of osteoarthritis (OA). This study was designed to determine the changes in the matrix composition of morphologically intact cartilage and meniscus during the acute phase of an anterior cruciate ligament (ACL) rupture, as well as the effect of different states of meniscus (intact or tear) on adjacent cartilage during the acute phase. Methods: This cross‐sectional study compared and analyzed 50 patients in the acute phase of ACL rupture who underwent surgical treatment and 66 age‐, weight‐ and height‐matched healthy volunteers from May 2022 to May 2023 at our institution. Mean T2 relaxation times and effect sizes in different regions of tibiofemoral articular cartilage and meniscus were compared between the two groups using the Mann–Whitney nonparametric t‐test, and correlations between different meniscal states and adjacent cartilage were analyzed. Results: Both in the lateral and medial compartments of the knee, T2 relaxation times were significantly higher in all subregions of cartilage and meniscus in the ACL rupture group (p < 0.05), and the site of injury was predominantly centered in the medial compartment (femur, p = 0.000; tibia, p = 0.000; anterior horn, p = 0.000). In the respective compartments, the posterior horn of the lateral meniscus showed a significant positive correlation with the mid‐cartilage of the femoral and tibial (r = 0.566, p = 0.035; r = 0.611, p = 0.02); and the posterior horn of the medial meniscus showed a significant positive correlation with the posterior tibial cartilage (r = 0.668, p = 0.018). Conclusion: During the acute phase of ACL rupture, the internal composition of the cartilage and meniscus undergoes significant changes, even if the morphology is intact. More importantly, the state of the meniscus significantly affects the internal composition of the adjacent cartilage. This is an early warning sign of OA, which should be closely monitored and carefully managed in clinical practice. [ABSTRACT FROM AUTHOR]

OBJECTIVE To describe the development and maturation of equine proximal sesamoid bones (PSBs) in fetuses and young horses using radiography, microcomputed (micro)-CT, and histology. METHODS A descriptive study. Forelimb PSBs from 12 equids ranging in age from 105 days of gestation to 540 days postgestation were evaluated. Radiography was used for preliminary assessment of metacarpophalangeal joint and PSB mineralization, and micro-CT imaging was performed to assess mineralized PSBs. Tissue volume, bone volume fraction, height, width, depth, trabecular thickness, and anisotropy were quantified from midplanar micro-CT sections in 3 dimensions. Midsagittal PSB histologic sections stained with H&E and Safranin O/Fast Green were used to determine the ratio of ossification center to cartilage template size and to describe the formation and development of the cartilage template, ossification center, spherical growth plate, articular cartilage, and entheses. RESULTS Mineralization of equine PSBs is associated with cartilage canals and a spherical growth plate that undergoes endochondral ossification during the late gestation to early postgestational period. The apical, flexor, basilar, and articular ossification fronts demonstrate morphologic variability. Structural organization of the articular cartilage and entheses occurs concurrently with the development of an underlying plate of compact bone. At 540 days postgestation, the fibrocartilaginous entheses of the flexor cortex of the PSB had yet to mature. CONCLUSIONS Equine PSBs mineralize predominantly by endochondral ossification during the late gestation to early postgestational period. Mineralization precedes maturation of the articular cartilage and fibrocartilaginous entheses. CLINICAL RELEVANCE The postgestational maturation of the PSB and its surrounding tissues may predispose young horses to developing lesions at these sites, such as apical avulsion fractures, warranting further investigation. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disease with an unclear cause characterized by secondary osteophytes and degenerative changes in the articular cartilage. More than 250 million people are expected to be affected by it by 2050, putting a tremendous socioeconomic strain on the entire world. OA cannot currently be treated with any effective medications that change the illness. Over time, chondrocytes undergo gradual metabolic, structural, and functional changes as a result of aging or abuse. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte homeostasis. By continuously recycling and rebuilding macromolecules or organelles, autophagy functions as a crucial regulatory system to maintain homeostasis during an individual's growth and development. This review uses chondrocytes as its starting point and establishes a strong connection between autophagy and osteoarthritis in order to thoroughly examine the mechanisms behind chondrocyte autophagy in osteoarthritis. Biomarkers of chondrocyte autophagy will be identified, and prospective targeted medications and novel treatment approaches for slowing or preventing the course of OA will be developed based on chondrocyte senescence, autophagy, and apoptosis in OA. Key messages: Currently, OA has not been treated with any drugs that can effectively cure it. We hope that by exploring specific targets in the course of osteoarthritis, we can promote the progress of treatment strategies. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte balance. Through the continuous recovery and reconstruction of macromolecules or organelles, autophagy is an important regulatory system for maintaining homeostasis during individual growth and development. In this paper, the close relationship between autophagy and osteoarthritis was established with chondrocytes as the starting point, in order to further explore the mechanism of chondrocyte autophagy in osteoarthritis. The development process of osteoarthritis was studied from the perspective of chondrocytes, and the change of autophagy level had a significant impact on osteoarthritis. Chondrocyte autophagy is mainly determined by intracellular mitochondrial autophagy, so we are committed to finding relevant molecules. Through PI3K/AKT- and MAPK-related pathways, the biomarkers of chondrocyte autophagy were identified, and chondrocyte senescence, autophagy, and apoptosis based on osteoarthritis provided a constructive idea for the development of prospective targeted drugs and new therapies to slow down or prevent the progression of osteoarthritis. [ABSTRACT FROM AUTHOR]

To provide a better understanding of the contribution of specific constituents (i.e. proteoglycan, collagen, fluid) to the mechanical behavior of the superficial zone of articular cartilage, a complex biological tissue with several time-dependent properties, a finite element model was developed. Optimization was then used to fit the model to microindentation experiments. We used this model to compare superficial zone material properties of mature human vs. immature bovine articular cartilage. Non-linearity and stiffness of the fiber-reinforced component of the model differed between human and bovine tissue. This may be due to the more complex collagen architecture in mature tissue and is of interest to investigate in future work. [ABSTRACT FROM AUTHOR]

Due to the absence of blood vessels and nerves, the regenerative potential of articular cartilage is significantly constrained. This implies that the impact of a ruptured cartilage extends to the entire joint. Osteoarthritis, a health condition, may arise due to injury and the progressive breakdown of joint tissues. The progression of osteoarthritis can be accelerated by the extensive degradation of articular cartilage, which is ranked as the third most prevalent musculoskeletal disorder necessitating rehabilitation, following low back pain and fractures. The existing therapeutic interventions for cartilage repair exhibit limited efficacy and seldom achieve complete restoration of both functional capacity and tissue homeostasis. Emerging technological advancements in the field of tissue engineering hold significant promise for the development of viable substitutes for cartilage tissue, capable of exhibiting functional properties. The overarching strategy involves ensuring that the cell source is enriched with bioactive molecules that facilitate cellular differentiation and/or maturation. This review provides a comprehensive summary of recent advancements in the field of cartilage tissue engineering. Additionally, it offers an overview of recent clinical trials that have been conducted to examine the latest research developments and clinical applications pertaining to weakened articular cartilage and osteoarthritis. [ABSTRACT FROM AUTHOR]

The good lubrication ability of articular cartilage holds significant importance in our daily lives. Osteoarthritis (OA), the most prevalent degenerative joint disease, causes cartilage damage, increased friction, and inflammation. However, the current clinical treatments for OA exhibit some defects. Recently, the sustained drug release systems with lubricating function have attracted considerable attention for treating OA. This review introduces the lubrication mechanism of cartilage, focusing particularly on the boundary lubrication mechanism. The research progress of boundary-lubricated biomaterials with drug delivery, including microcarriers, hydrogels, and nanoparticles in the treatment of OA by improving inter-articular lubrication and relieving inflammation is discussed and summarized. The efficacy and challenges of boundary-lubricated biomaterials with drug delivery in the treatment of OA are summarized, and the prospects are also discussed. [ABSTRACT FROM AUTHOR]

Medial unicompartment knee replacement (UKR) is performed for isolated medial compartment osteoarthritis. Understanding the factors influencing functional outcomes helps patient selection and outcomes. We will review the association between pre-operative BMI and patellofemoral articular wear on post operative Oxford Knee Scores at >2 and > 5 years. A retrospective review of a prospectively collected database was performed. Inclusion criteria were medial UKR for medial compartment OA. The exclusion criteria were age <16, revision procedures and lateral UKR's. Data was collected between 26/6/2014 and 25/8/2022. Statistical analysis was performed using SPSS. Significance was given to variables that reached p < 0.05. 159 UKR procedures were identified in 155 patients. 116 procedures carried out on 111 patients had follow up at > 2 years. At 5 years there were 14 patients had OKS recorded. There was no statistical difference in the ICRS grade I&II vs III&IV groups for >2 year or >5 year OKS with p = 0.408 and p = 0.876. For BMI there was a moderately negative correlation on spearman's rank p(df) = -0.339 (CI 95 % −0.538, −0.104) at >2 years, which was statistically significant with p = 0.004. >5 year data didn't reach significance with p = 0.828. BMI maybe an important patient factor in predicting post operative OKS at 2–5 years. This is beneficial to surgeons for patient selection in medial UKR. Patellofemoral wear doesn't appear to impact on post operative functional outcomes. This supports the theory that patient who suffer from patellofemoral wear, as well as medial compartment wear can benefit from UKR, expanding the current indications. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the effects of microfracture (MF) versus intra-articular hyaluronic acid (HA) + oral glucosamine and chondroitin sulfate (GC) in addition to MF in patients with osteoarthritic knees who underwent medial open wedge high tibial osteotomy (MOWHTO) after an average follow-up of five years. Methods: The study was designed retrospectively and included patients who underwent MOWHTO due to gonarthrosis, the MF method performed on these patients, and HA + GC treatments applied in addition to MF. Three groups consisting of 79 patients were formed: only HTO (Group 1), HTO + MF (Group 2), and HTO + MF + HA + GC (Group 3). The groups were compared using knee injury and osteoarthritis outcome score (KOOS), visual analog scale (VAS) for pain, and range of motion (ROM). The associations between the degree of correction and function and pain were evaluated. Additionally, the KOOS subparameters were compared between the groups. Results: There were significant improvements in the postoperative KOOS and VAS scores in all three groups (p < 0.05). However, the ROM did not improve in Group 1. There was no significant difference in the postoperative KOOS, VAS, or ROM values ​​between Groups 2 and 3, but these values ​​were significantly better in Groups 2 and 3 than in Group 1 (p < 0.05). When the degree of correction increased, there were no significant positive changes in the postoperative KOOS or VAS score in Group 1, unlike in the other two groups (p < 0.05). In corrections of ≥ 10°, while there was no significant difference in the postoperative KOOS or VAS score ​​between Groups 2 and 3, these parameters significantly improved in these two groups compared to Group 1 (p < 0.05). Among the KOOS subparameters, pain and activities of daily living scores ​​were greater in Groups 2 and 3 than in Group 1 (p < 0.05). Conclusions: In MOWHTO, MF is a sufficient treatment method that improves the patient's clinical condition without requiring additional treatments such as HA and GC. Level of evidence: III, retrospective cohort study. [ABSTRACT FROM AUTHOR]

AbstractOsteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_0128006 (also known as circSEC24) was reported as an upregulated circRNA in OA tissues, but its biological role and underlying mechanism in OA are still to be discussed. circSEC24A and NAMPT expression levels were upregulated, and miR-515-5p was reduced in OA cartilage tissues and IL-1β-treated CHON-001 cells. The absence of circSEC24A overturned IL-1β-induced suppression of cell viability and promotion of oxidative stress, apoptosis, extracellular matrix (ECM) degradation, and inflammation in CHON-001 cells. Mechanistically, circSEC24A acted as a molecular sponge for miR-515-5p to affect NAMPT expression. CircSEC24A knockdown could attenuate IL-1β-triggered CHON-001 cell injury partly via the miR-515-5p/NAMPT axis, providing new insight into the underlying application of circSEC24A in OA treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to the very limited ability of articular cartilage to repair itself, articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own, which triggers or aggravates osteoarthritis and even leads to severe disability. Therefore, the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE: To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS: Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023, and bibliometric and visualization analyses were carried out using VOSviewer, Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION: The annual publication volume in the field of articular cartilage repair shows an overall increasing trend, with the United States, China, and Germany being the top three countries in terms of publication volume, and the research institutions focus on universities and hospitals, with Harvard University, New York Hospital for Special Surgery, and Shanghai Jiao Tong University being the top three institutions in terms of publication volume. AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field, and BIOMATERIALS is the journal with the highest number of citations in the field. “Injectable hydrogels for cartilage and bone tissue engineering” is the most cited document published in the last decade, and the author with the most publications is Madry Henning, an active author in the field. The active authors in this field have formed a number of stable research teams with each other, and the cooperation between different teams needs to be further strengthened. Intra-articular injections, high tibial osteotomies, hydrogels, drug delivery, inflammation, cartilage regeneration, and scaffolds are the current hot topics of research in this field, and the application of 3D printing technology, bio-inks, silk proteins, injectable hydrogels, and exosomes in articular cartilage repair may be the frontier of research in this field. Integrating various innovative technologies and methods for more effective, durable and functional cartilage tissue regeneration and repair, and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field. [ABSTRACT FROM AUTHOR]

Background: Moderate mechanical stress generated by normal joint loading and movements helps maintain the health of articular cartilage. Despite growing interest in the pathogenesis of cartilage degeneration caused by reduced mechanical stress, its reversibility by mechanical reloading is less understood. This study aimed to investigate the response of articular cartilage exposed to mechanical reloading after unloading in vivo and in vitro. Methods and results: Disuse atrophy was induced in the knee joint cartilage of adult mice through hindlimb unloading by tail suspension. For in vivo experiments, mice were subjected to reloading with or without daily exercise intervention or surgical destabilization of the knee joint. Microcomputed tomography and histomorphometric analyses were performed on the harvested knee joints. Matrix loss and thinning of articular cartilage due to unloading were fully or partially restored by reloading, and exercise intervention enhanced the restoration. Subchondral bone density decreased by unloading and increased to above-normal levels by reloading. The severity of cartilage damage caused by joint instability was not different even with prior non-weight bearing. For in vitro experiments, articular chondrocytes isolated from the healthy or unloaded joints of the mice were embedded in agarose gel. After dynamic compression loading, the expression levels of anabolic (Sox9, Col2a1, and Acan) and catabolic (Mmp13 and Adamts5) factors of cartilage were analyzed. In chondrocytes isolated from the unloaded joints, similar to those from healthy joints, dynamic compression increased the expression of anabolic factors but suppressed the expression of catabolic factors. Conclusion: The results of this study indicate that the morphological changes in articular cartilage exposed to mechanical unloading may be restored in response to mechanical reloading by shifting extracellular matrix metabolism in chondrocytes to anabolism. [ABSTRACT FROM AUTHOR]

The repair of articular cartilage after damage is challenging, and decellularized tissue offers a possible treatment option to promote regeneration. Here, we show that acellular osteochondral allografts improve integrative cartilage repair compared to untreated defects after 6 months in an ovine model. Functional measures of intratissue strain/structure assessed by MRI demonstrate similar biomechanics of implants and native cartilage. Compared to native tissue and defects, the structure, composition, and tribology of acellular allografts preserve surface roughness and lubrication, material properties under compression and relaxation, compositional ratios of collagen:glycosaminoglycan and collagen:phosphate, and relative composition of types I/II collagen. While high cellularity was observed in bone regions and integration zones between cartilage-allografts, recellularization of chondral implants was inconsistent, with cell migration typically less than ~750 µm into the dense decellularized tissue, possibly limiting long-term cellular maintenance. Our results demonstrate the structural and biomechanical efficacy of acellular allografts for at least six months in vivo. [ABSTRACT FROM AUTHOR]

Articular cartilage is a tissue with relatively poor self‐regeneration capacity due to insufficient blood vessels and chondrocytes in the region. Biomaterial‐assisted tissue engineering has shown great potential in cartilage regeneration. However, there are still many worries over the uses of exogenous growth factors, stem cells and scaffolds. To address these concerns, here a dynamic proteinaceous hydrogel with a self‐recruiting ability of cartilage‐inducing factor for in situ cartilage regeneration is reported. The dynamic hydrogel (Pep‐GelSH) is prepared by using thiol‐modified gelatin and thiol‐capped TGF‐β1‐affinity peptide through the Au‐S coordination. The injectability and self‐recovery of Pep‐GelSH hydrogel enabled not only minimally invasive implantation but also the adaptability of the scaffold to irregular defect shapes. Meanwhile, the dynamic hydrogel showed improved adherence to the host tissue and allowed quick infiltration of host cells. More importantly, the hydrogel significantly enhanced local enrichment of endogenous TGF‐β1 and led to the recruitment of stem cells in vivo. After implantation, the hydrogel scaffold triggered the innate repair capacity of cartilage defects by successively promoting stem cells recruitment, infiltration and differentiation, resulting in significantly enhanced chondrogenesis and improved cartilage repair. Therefore, the study in this work may provide a feasible and promising approach for in situ cartilage regeneration. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is defined by articular cartilage degeneration, synovial membrane inflammation, and abnormal bone remodeling. Recent study has discovered that OA development is linked to an aberrant epigenetic modification of OA‐related genes. Our previous research showed that DNA demethylation in ADAMTS‐5 promoter region had a substantial impact on ADAMTS‐5 expression in the mouse OA model. This process facilitated the binding of Spi‐1 to ADAMTS‐5 promoter. While alterations in histone methylation have been documented during embryonic development and cancer development, there is a paucity of data on the change in OA pathogenesis. Even no data have been reported on the role of histone modifications in ADAMTS‐5 activation in OA. Following our previous study on the role of DNA methylation, we aimed to examine the contribution of histone H3K9 dimethylation in ADAMTS‐5 activation in OA. Additionally, we aimed to elucidate the molecular mechanisms underlying the cooperative interaction between DNA methylation and histone H3K9 dimethylation. The potential for anti‐OA intervention therapy which is based on modulating histone H3K9 dimethylation is also explored. We demonstrated that a reduction in histone H3K9 dimethylation, along with DNA demethylation of the Spi‐1 binding site, had a role in ADAMTS‐5 activation in the articular cartilage of OA mice. Significantly, the conditional deletion of histone demethylase to be identified as lysine‐specific demethylase 1 (LSD1) in articular cartilage could alleviate the degenerative features of OA mice. Our study demonstrates the direct impact of histone H3K9 dimethylation on gene expression, which in turn contributes to OA development. This research enhances our understanding of the underlying causes of OA. [ABSTRACT FROM AUTHOR]

Joint injury can lead to articular cartilage damage, excessive inflammation, and post‐traumatic osteoarthritis (PTOA). Collagen is an essential component for cartilage function, yet current literature has limited understanding of how biochemical and biomechanical factors contribute to collagen loss in injured cartilage. Our aim was to investigate spatially dependent changes in collagen content and collagen integrity of injured cartilage, with an explant model of early‐stage PTOA. We subjected calf knee cartilage explants to combinations of injurious loading (INJ), interleukin‐1α‐challenge (IL) and physiological cyclic loading (CL). Using Fourier transform infrared microspectroscopy, collagen content (Amide I band) and collagen integrity (Amide II/1338 cm−1 ratio) were estimated on days 0 and 12 post‐injury. We found that INJ led to lower collagen content near lesions compared to intact regions on day 0 (p < 0.001). On day 12, near‐lesion collagen content was lower compared to day 0 (p < 0.05). Additionally, on day 12, INJ, IL, and INJ + IL groups exhibited lower collagen content along most of tissue depth compared to free‐swelling control group (p < 0.05). CL groups showed higher collagen content along most of tissue depth compared to corresponding groups without CL (p < 0.05). Immunohistochemical analysis revealed higher MMP‐1 and MMP‐3 staining intensities localized within cell lacunae in INJ group compared to CTRL group on day 0. Our results suggest that INJ causes rapid loss of collagen content near lesions, which is intensified on day 12. Additionally, CL could mitigate the loss of collagen content at intact regions after 12 days. [ABSTRACT FROM AUTHOR]