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Musculoskeletal disorders are the most common reason of chronic pain and disability representing worldwide an enormous socio-economic burden. In this review, new biomedical application fields for Raman spectroscopy (RS) technique related to skeletal tissues are discussed showing that it can provide a comprehensive profile of tissue composition in situ, in a rapid, label-free, and non-destructive manner. RS can be used as a tool to study tissue alterations associated to aging, pathologies, and disease treatments. The main advantage with respect to currently applied methods in clinics is its ability to provide specific information on molecular composition, which goes beyond other diagnostic tools. Being compatible with water, RS can be performed without pre-treatment on unfixed, hydrated tissue samples, without any labelling and chemical fixation used in histochemical methods. This review provides first the description of basic principles of RS as a biotechnology tool and introduces into the field of currently available RS based techniques, developed to enhance Raman signal. The main spectral processing statistical tools, fingerprint identification and available databases are mentioned. The recent literature has been analysed for such applications of RS as tendon and ligaments, cartilage, bone, and tissue engineered constructs for regenerative medicine. Several cases of proof-of-concept preclinical studies have been described. Finally, advantages, limitations, future perspectives, and challenges for translation of RS into clinical practice have been also discussed.

Local-area cartilage segmentation (LACS) software was developed to segment medial femur (MF) cartilage on magnetic resonance imaging (MRI). Our objectives were 1) to extend LACS to the lateral femur (LF), medial tibia (MT), and lateral tibia (LT), 2) to compare LACS to an established manual segmentation method, and 3) to visualize cartilage responsiveness over each cartilage plate.Osteoarthritis Initiative participants with symptomatic knee osteoarthritis (OA) were selected, including knees selected at random (n = 40) and knees identified with loss of cartilage based on manual segmentation (Chondrometrics GmbH), an enriched sample of 126 knees. LACS was used to segment cartilage in the MF, LF, MT, and LT on sagittal 3D double-echo steady-state MRI scans at baseline and at 2-year follow-up. We compared LACS and Chondrometrics average thickness measures by estimating the correlation in each cartilage plate and estimating the standardized response mean (SRM) for 2-year cartilage change. We illustrated cartilage loss topographically with SRM heatmaps.The estimated correlation between LACS and Chondrometrics measures was r = 0.91 (95% confidence interval [95% CI] 0.86, 0.94) for LF, r = 0.93 (95% CI 0.89, 0.95) for MF, r = 0.97 (95% CI 0.96, 0.98) for LT, and r = 0.87 (95% CI 0.81, 0.91) for MT. Estimated SRMs for LACS and Chondrometrics measures were similar in the random sample, and SRM heatmaps identified subregions of LACS-measured cartilage loss.LACS cartilage thickness measurement in the MF and LF and tibia correlated well with established manual segmentation-based measurement, with similar responsiveness to change, among knees with symptomatic knee OA. LACS measurement of cartilage plate topography enables spatiotemporal analysis of cartilage loss in future knee OA studies.

For the treatment of the moderate leg length discrepancy (2–6 cm) in children surgeons use temporal growth plate (GP or epiphyseal cartilage) block with plates and screws. Objective: to study morphological changes in distal femur growth plate of rabbits under bilateral temporal block with non-locking plates and screws. Methods: we blocked distal GP of the right femur of 9 rabbits (8 weeks old). On 3rd, 5th and 7th weeks histological study of the distal femoral growth plate of both femurs with morphometry was made. Results: in 3rd weeks after surgery the height of the GP on the operated side was decreased in lateral and medial parts in 2.06 and 1.98 times (p, Для лечения умеренной разницы (2–6 см) длины нижних конечностей у детей используют временное блокирование зоны роста (ЗР или эпифизарный хрящ) пластинами с винтами.Цель: исследовать морфологические изменения ЗР дистального отдела бедренной кости кроликов при ее двустороннем блокировании неблокируемыми пластинами с винтами.Методы: блокировали дистальную ЗР правой бедренной кости 9 кроликов в возрасте 8 нед. Через 3, 5 и 7 нед. выполнен гистологический анализ (с морфометрией) дистальных отделов обеих бедренных костей.Результаты: через 3 нед. после операции высота кости с блокированием была сниженной в латеральном и медиальном отделах в 2,06 и 1,98 раза (p, Для лікування помірної різниці (2–6 см) довжини нижніх кінцівок у дітей використовують тимчасове блокування наросткової зони (НЗ або епіфізарний хрящ) пластинами з гвинтами.Мета: дослідити морфологічні зміни НЗ дистального відділу стегнової кістки кроликів в умовах її двобічного блокування неблокованими пластинами з гвинтами.Методи: блокували дистальну НЗ правої стегнової кістки 9 кроликів у віці 8 тижнів. Через 3, 5 і 7 тижнів виконаний гістологічний аналіз (з морфометрією) дистальних відділів обох стегнових кісток.Результати: через 3 тижні після операції висота кістки з блокуванням була зниженою в латеральному та медіальному відділах у 2,06 і 1,98 разу (p

Posterior ankle impingement syndrome is mainly seen in ballet dancers and frequently associated with specific movements in ballet such as pointe and demi pointe in which the whole-body weight is applied to the maximally plantar flexed ankle. We performed arthroscopic debridement for 2 dedicated ballet dancers on the intervening soft tissue causing posterior ankle impingement syndrome (PAIS). In both cases, T2-weighted magnetic resonance imaging (MRI) revealed low-signal intensity of meniscus-like soft tissue without abnormal osseous findings, connecting from the posterior side of the talus to Kager's fat pad. To examine the intervening soft tissue in detail, we performed histological evaluation by hematoxylin and eosin staining, Safranin O fast green staining, and immunohistochemistry for type I collagen and type II collagen. Hematoxylin and eosin staining showed that there was cartilage-like tissue including chondrocyte-like cells in contact with fibrous tissue. The extracellular matrix in the cartilage zone was consistently stained by Safranin O staining and type II collagen without any staining with type I collagen. These findings suggested that the meniscus-like soft tissue appearing as low-signal intensity on MRI at the posterior side of talus included hyaline-like cartilage. To the extent of our knowledge, these were rare cases of hyaline-like cartilage generation causing PAIS in ballet dancers, which might be associated with ballet specific movements resulting in chondrogenesis.

BACKGROUND: Lesions of articular cartilage represent a crucial risk factor for the early development of osteoarthritis. Autologous chondrocyte implantation (ACI) is a well-established procedure in therapy of those lesions in the knee. The aim of the presented study is to detect differences in short-term radiological outcome depending on defect localization (femoral condyle vs. retropatellar) after spheroid-based ACI. OBJECTIVE: This study aimed to demonstrate that radiological outcome after spheroid-based ACI in the knee is independent of defect localization. METHODS: MRI-scans after retropatellar ACI and ACI of the medial/lateral femoral condyle, with a preoperative Outerbridge grade of III or IV were evaluated regarding MOCART 2.0. RESULTS: The mean defect-size was 5.0 ± 1.8 cm2, with a minimum size of 2 cm2 and a maximum size of 9 cm2. Scans were performed 7.7 months (± 3.1 months) postoperatively. The mean MOCART 2.0 score was 78.5 ± 15.6. No statistically significant influence neither of the localization (p= 0.159), the gender (p= 0.124) nor defect size (< 5 cm2 vs. ⩾ 5 cm2; p= 0.201) could be observed. CONCLUSIONS: The presented data demonstrate good to excellent radiological short-term results after spheroid-based ACI. Data indicates, that at least radiological results are independent of gender, defect-size and defect-localization.

Purpose The purpose of this study was to determine whether radiographic parameters, intraoperative findings, patient-reported outcome measures, or intraoperative interventions that were performed differentiate those patients with >2 mm of joint space who convert under two years to total hip arthroplasty (THA) after undergoing hip arthroscopy for femoroacetabular impingement (FAI) when compared to those converting after 2 years. Methods Included in this study were patients who underwent conversion to THA within 2 years of primary hip arthroscopy from a prospectively collected patient registry from 2007 to 2017. Patients who underwent early conversions to arthroplasty were matched 1:1 with patients who converted after 2 years, based upon age and gender. Preoperative outcome scores were collected, including Short Form-12, modified Harris Hip Score, and Hip Outcome Score. Additionally, variables from the preoperative radiographic evaluation, surgical findings, and procedures performed were also compared. Results Forty-nine patients were included in the early conversion group and were matched with 49 patients in the later conversion group. Patients with lateral center edge angles of less than 25° were more likely to be in the early failure group [OR: 3.9; 95% CI: 1.01 to 15]. Patients with unipolar chondral defects on either the femoral (P = .128) or acetabular side (P = .656) were not at increased odds for early conversion compared to later conversion; however, those with bipolar chondral lesions at the time of surgery had increased odds of early conversions [OR: 3.3; 95% CI: 1.4 to 8] (P = .01). Neither surgical treatment nor preoperative patient-reported outcome measures were associated with early conversion. Conclusions In patient with >2 mm of joint space, lateral center edge angles of less than 25° and those with bipolar articular cartilage lesions seen at the time of hip arthroscopy are at increased risk for conversion to total hip arthroplasty within two years. Level of Evidence Level III, retrospective comparison study.

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which — once applied to human neutrophils — attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor–deficient mice termed ALX/fpr2/3–/–. These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA., The lipid mediator resolvin D1 attenuates arthritis severity, limits joint leukocyte infiltration, and promotes cartilage protection.

Purpose To analyze the in vivo tibiofemoral cartilage contact patterns in knees undergoing double-bundle anterior cruciate ligament reconstruction(DB-ACLR) with or without anterolateral structure augmentation (ALSA). Methods Twenty patients with an ACL-ruptured knee and a healthy contralateral side were included. Nine patients received an isolated DB-ACLR (DB-ACLR group), and 11 patients had a DB-ACLR with ALSA (DB+ALSA group). At 1-year follow-up, a combined computed tomography, magnetic resonance imaging, and dual fluoroscopy imaging system analysis was used to capture a single-legged lunge of both the operated and healthy contralateral side. Tibiofemoral contact points (CPs) of the medial and lateral compartments were compared. CP locations were expressed as anteroposterior (AP, +/–) and medial–lateral (ML, –/+) values according to the tibia. Results In the DB-ACLR knees, no significant differences were found in CPs when compared with the healthy contralateral knees (P ≥ .31). However, in the DB+ALSA knees, the CPs in the lateral compartment had a significantly more anterior (mean AP: operative, –2.8 mm, 95% confidence interval [CI] –5.0 to–0.7 vs healthy, –5.0 mm, 95% CI –6.7 to –3.2; P = .006) and lateral (mean ML: operative, 23.2 mm, 95% CI 21.9-24.5 vs healthy, 21.8 mm, 95% CI 20.2-23.3; P = .013) location. The CPs in the medial compartment were located significantly more posterior (mean AP: operative, –3.4, 95% CI –5.0 to –1.9 vs healthy, –1.3, 95% CI –2.6 to –0.1; P = .006) and lateral (mean ML: operative, –21.3, 95% CI –22.6 to –20.0 vs healthy, –22.6, 95% CI –24.2 to –21.0; P = .021). Conclusions DB-ACLR restored the tibiofemoral cartilage contact mechanics to near-normal values at 1-year follow-up. Adding the ALSA to the DB-ACLR resulted in significantly altered tibiofemoral cartilage contact locations in both the medial and lateral compartments. Clinical Relevance In DB-ACLR knees, the addition of an ALSA may be unfavorable as it caused significantly changed arthrokinematics.

Summary Objective Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model. Methods Peripheral Syx was generated by 6-hydroxydopamine (6-OHDA) injections in male C57BL/6 mice. OA was induced in wild-type (WT) and Syx mice by destabilization of the medial meniscus (DMM). TH+ fibers and splenic NE were analyzed to evaluate Syx efficiency. OA progression was examined by OARSI and synovitis scores and micro-CT. Expression of TH, α2A- and β2-adrenergic receptors (AR), and activity of osteoblasts (ALP) and osteoclasts (TRAP) was investigated by stainings. Results Syx resulted in synovial TH+ fiber elimination and splenic NE decrease. Cartilage degradation and synovitis after DMM were comparably progressive in both WT and Syx mice. Calcified cartilage (CC) and subchondral bone plate (SCBP) thickness and bone volume fraction (BV/TV) increased in Syx mice due to increased ALP and decreased TRAP activities compared to WT 8 weeks after DMMWT and Syx mice developed osteophytes and meniscal ossicles without any differences between the groups. AR numbers decreased in cartilage but increased in synovium and osteophyte regions after DMM in both WT and Syx mice. Conclusion Peripheral dampening of SNS activity aggravated OA-specific cartilage calcification and subchondral bone thickening but did not influence cartilage degradation and synovitis. Therefore, SNS might be an attractive target for the development of novel therapeutic strategies for pathologies of the subchondral bone.

Summary Objective To develop a machine learning-based prediction model for incident radiographic osteoarthritis (OA) of the knee over 8 years using MRI-based cartilage biochemical composition and knee joint structure, demographics, and clinical predictors including muscle strength and symptoms. Design Individuals (n=1044) with baseline Kellgren Lawrence (KL) grade 0-1 in the right knee from the Osteoarthritis Initiative database were analyzed. 3T MRI at baseline was used to quantify knee cartilage T2, and Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone marrow. The outcome was set as true if a subject developed KL grade 2-4 OA in the right knee over 8 years (n=183) and false if the subject remained at KL 0-1 over 8 years (n=861). We developed and compared three models: Model 1: 112 predictors based on OA risk factors; Model 2: top ten predictors based on feature importance score from Model 1 and clinical relevance; Model 3: Model 2 without the imaging predictors. We compared the models using the area under the R OC curve derived from hold-out data. Results The 10-predictor model (Model 2, that includes cartilage and meniscus WORMS scores and cartilage T2) had a slightly lower AUC (0.772) compared to the model with 112 predictors (Model 1: AUC=0.792, p=0.739); and had a significantly higher AUC compared to the model without MR imaging predictors (Model 3, AUC=0.669, p=0.011). Conclusions A 10-predictor model including MRI parameters coupled with demographics, symptoms, muscle, and physical activity scores provides good prediction of incident radiographic OA over 8 years.

Background This study aims to explore whether Fufang Shatai Heji (STHJ), as a mixture collected by a decoction of a variety of Chinese herbal medicines for immune system diseases, can improve the cartilage destruction of rheumatoid arthritis (RA). Methods The therapeutic effects of STHJ were studied using collagen induced arthritis (CIA) mice. The improvement effect of STHJ on synovitis and cartilage damage caused by arthritis was studied by joint pathological analysis. The inhibitory effect of STHJ on related degradation enzymes in cartilage was studied by immunohistochemistry and real-time polymerase chain reaction (PCR). The specific targets of STHJ were predicted by molecular docking. Results After successfully inducing CIA, the paws of the mice showed significant swelling, and athological analysis of the ankle and knee joints also showed significant cartilage destruction and synovial hyperplasia. However, synovial hyperplasia and cartilage destruction were markedly alleviated after administration of STHJ. And after SHTJ treatment, the expression of ADAMTS-4, ADAMTS-5, MMP-9 and MMP-13, in the cartilage layer of CIA mice was significantly inhibited. Through molecular docking assays, we proved that acteoside in STHJ could directly bind to the Glu111, Phe110 residues in MMP-9 and glycyrrhizic acid in STHJ bind to the Glu382, Asn433 residues in MMP-13. Conclusions Our results suggested that STHJ may alleviate synovial hyperplasia and cartilage destruction in CIA mice and protect cartilage by inhibiting the expression of MMP-9 and other enzymes.

Osteoarthritis (OA) is the most common degenerative disease in older adults and its treatment remains unsatisfactory. This study aimed to evaluate the effectiveness and explore the therapeutic mechanisms of the combination of platelet-rich plasma (PRP) and ozone (O3) for knee OA.Thirty male rabbits were randomly divided into five groups (Control group, OA group, PRP group, O3 group, and PRP + O3 group). Rabbit model of OA were induced by improved Hulth surgery. Gross articular observation, histopathological examination and cartilage scoring system were used to assess the articular cartilage destruction. The bone morphogenetic protein-2 (BMP-2) mRNA expression in joint fluid was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of type II collagen, matrix metalloproteinase-1 (MMP-1) of cartilage was detected via Immunohistochemistry. Pain behavior was observed by percent ipsilateral weight-bearing (PIW) asymmetry.The content of platelet in PRP was increased by 6.2-times that in whole blood. Among induced OA groups (the OA, PRP, O3 and PRP + O3 group), PRP + O3 significantly inhibited the surgically induced increase in gross articular alterations, histopathological damage of cartilage and Mankin score when compared to the OA, PRP and O3 groups (P0.05). Observed pain behavior by weight-bearing asymmetry, in the PRP + O3 group was reversed at 3 and 6 weeks after the administration of PRP + O3 (PIW asymmetry: -10.66%±1.172%). In addition, surgery-induced BMP-2 mRNA expression was significantly downregulated after the treatment of PRP, O3 and PRP + O3 (P0.01). PRP + O3 group significantly increased the expression of type II collagen but decreased MMP-1 of cartilage in comparison to OA, PRP and O3 groups (P0.05) by immunohistochemical analysis.PRP combined with O3 may prevent cartilage destruction and improve weight-bearing asymmetry by restoring homeostasis between anabolism and catabolism of extracellular matrix in progressive OA. Furthermore, a combination of PRP and O3 might achieve even better results than the two agents alone.

Summary Objective Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known. Design To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools. Results We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS. Conclusion These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the hip, including osteonecrosis (aseptic necrosis) involving bone marrow, bone, and cartilage, and chondral injuries involving articular cartilage, synovium, and bone marrow. Promising and established treatment modalities for osteonecrosis include nonweightbearing; pharmacological treatments including low molecular-weight heparin, prostacyclin, statins, bisphosphonates, and denosumab, a receptor activator of nuclear factor-kB ligand inhibitor; extracorporeal shock wave therapy; pulsed electromagnetic fields; core decompression surgery; cellular therapies including bone marrow aspirate comprising mesenchymal stromal cells (MSCs aka mesenchymal stem cells) and bone marrow autologous concentrate, with or without expanded or cultured cells, and possible addition of bone morphogenetic protein-2, vascular endothelial growth factor, and basic fibroblast growth factor; and arterial perfusion of MSCs that may be combined with addition of carriers or scaffolds including autologous MSCs cultured with beta-tricalcium phosphate ceramics associated with a free vascularized fibula. Promising and established treatment modalities for chondral lesions include autologous platelet-rich plasma; hyaluronic acid; MSCs (in expanded or nonexpanded form) derived from bone marrow or other sources such as fat, placenta, umbilical cord blood, synovial membrane, and cartilage; microfracture or microfracture augmented with membrane containing MSCs, collagen, HA, or synthetic polymer; mosaicplasty; 1-stage autologous cartilage translation (ACT) or 2-stage ACT using 3-dimensional spheroids; and autologous cartilage grafting; chondral flap repair, or flap fixation with fibrin glue. Hip pain is catastrophic in young patients, and promising therapies offer an alternative to premature arthroplasty. This may address both physical and psychological components of pain; the goal is to avoid or postpone an artificial joint. Level of Evidence Level V, expert opinion.

Cellular therapy based on chondrocytes implantation is the most widely used procedure for inducing cartilage regeneration. However, the dedifferentiation process that these cells suffer and their limited capacity of proliferation, when they are cultured in vitro, restrict their use in cellular therapy protocols. To investigate the capacity of mesenchymal stromal cells (MSCs) to promote chondrogenesis from chondrocytes or chondrons in 2D and 3D coculture systems. Murine chondrocytes and chondrons were cocultured with MSCs at different cell ratios (100/0, 50/50, 70/30, 0/100) in two-dimensional (2D) and three-dimensional (3D) culture systems. High proliferation of cells with chondrocyte morphology, enhanced GAG production and expression of cartilage genes (aggrecan, type II collagen, and SOX-9) were observed in chondrocytes/MSCs cocultures. In contrast, fibroblastoid cells, down-regulation of cartilage gene expression and reduction of GAG production were observed in chondrons/MSCs cocultures. Chondrocytes within cartilage lacunae and surrounded by extracellular matrix were observed in chondrocytes/MSC pellets. MSCs promote the proliferation of functional chondrocytes in 2D and 3D culture systems. Transplantation of chondrogenic construct based on MSCs and chondrocytes may constitute a potential treatment for inducing cartilage repair.

Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.

Background Osteochondritis dissecans (OCD) is considered to show the following stages of pathological progression: IA, nearly normal-cartilaginous; IB, deteriorated-cartilaginous; IIA, cartilage-ossifying; and IIB, cartilage-osteonecrotic. However, the validity of this pathological staging for OCD has yet to be confirmed in a large number of cases. Purpose The aim of the present study was to confirm the clinical validity of the proposed pathological staging of OCD. Methods The subjects were 74 patients (mean age, 14.2 years; mean skeletal age score, 25.6 points) with capitellar OCD. Partially detached articular fragments were surgically removed, and were examined histologically. The articular fragments were independently assessed by five observers and the reliability of assessment was examined. The correlation between the pathological stages and the clinical data was analyzed. Results The reliability of the assessment among five observers was almost perfect. OCD stages of IA, IB, IIA, and IIB were evident in eight, 36, 10, and 20 patients, respectively. OCD-I (cartilaginous) and OCD-II (osteochondral) corresponded significantly to radiographic stage I (radiolucency) and stage II (delayed ossification), respectively. The pathological OCD stages were significantly correlated with the clinical data, including the period from symptom onset to surgery, patient age, and the skeletal age score (p Conclusion Our results confirmed that the proposed pathological staging of OCD corresponds to the observed clinical progression of OCD, thus validating the staging system. Our findings revealed that OCD begins with separation beneath the epiphyseal cartilage which is programmed to be replaced with bone. When a stage IA articular fragment has remained partially detached for a prolonged period, the epiphyseal cartilage may be deteriorated and become degenerated, and subsequent ossification may not occur, as is evident in OCD-IB. In contrast, stage IA with a vascular supply through the fibrocartilaginous connection can progress to stage IIA. During the prolonged period in which the osteochondral articular fragment remains un-united, microtrauma can cause to disturb the blood supply to the bony fragment, resulting in osteonecrosis (stage IIB).

Articular cartilage can be easily damaged from human's daily activities, leading to inflammation and to osteoarthritis, a situation that can diminish the patients' quality of life. For larger carti...

Deforming osteoarthritis of the shoulder joint — current and underinvestigated problem. One of the main factors in the development of arthrosis is a traumatic injury of the joint capsular ligaments, violation of joint mobility and inflammation. At the same time, the place of abnormal biomechanics remains unknown in the development of osteoarthritis of the shoulder joint as a monofactor of pathological condition. Objective: to investigate the role of limited biomechanics of the shoulder joint as a monopatogenetic factor in the development of osteoarthritis of the shoulder joint. Materials and methods. In the experiment, the model of osteoarthritis has been reproduced in guinea pigs, and the structural changes in the joint were investigated 3 months after. Cryosections were obtained from the decalcinated shoulder samples, histological and morphometric study was performed. Results and discussion. The structural damages of the articular surface of the humeral head and shoulder blade cavity were detected, as well as changes in the contour of the subchondral bone tissue, proliferative changes in the joint capsule. Disturbed mobility and altered zone of load caused the loss of 48 % (p < 0.01) of cartilage thickness in humeral articular surface and 14 % of the glenoid (p < 0.01). That is, a significant limitation of mobi-lity (biomechanics) of the shoulder joint leads to dystrophic changes of cartilage elements in both articular surfaces. Conclusions. Research results confirmed that impaired biomechanics of the shoulder joint movements is one of the monopatogenetic factors of osteoarthrosis.

Post-traumatic OA (PTOA) arises from joint injury, it accounts for a significant portion of patients with osteoarthritis. Intra-articular fractures associated with hemarthrosis, ruptures and rough damage to the meniscus, ligaments, cartilage injuries are the most common causes of PTOA. Damage to articular cartilage can occur in the period immediately after the injury, in the near future or develop several years after the injury. Even with appropriate treatment, such as rigid fixation of intra-articular fractures, reconstruction of damaged ligament with a successful restoration of joint biomechanics, the risk of PTOA ranges from 20 to more than 50 %. In the last decade, the role of inflammation in the development and progression of PTOA is being actively discussed and studied. Signs of inflammation may be observed in the joint fluid and tissues of patients with injuries of the joints and the risk of post-traumatic osteoarthritis. In addition, inflammatory mechanisms lead to the risk of developing osteoarthritis and its progression after injury. The development of PTOA involves molecular and cellular mechanisms. Synovium, articular cartilage and subchondral bone also react to the injury by changing metabolic activity and expression of inflammatory proteins. This review summarizes the results of recent studies of pathological mechanisms underlying PTOA development. This allows you to take a new look at the mechanisms of PTOA development, the role of inflammation in the progression of the disease, and to assess the limitations for early pharmacological intervention., Посттравматический остеоартрит (ПТОА) возникает при травме суставов, на его долю приходится значительная часть пациентов с остеоартритом (ОА). Внутрисуставные переломы, сопровождающиеся гемартрозом, разрывы и грубые повреждения менисков, связочного аппарата, травмы хрящевой ткани являются наиболее частыми причинами, ведущими к ПТОА. Повреждение суставного хряща может происходить в период сразу после травмы, в ближайшее время или развиваться через несколько лет после травмы. Даже при соответствующем лечении, таком, как жесткая фиксация внутрисуставных переломов, реконструкция поврежденных связок с успешным восстановлением биомеханики сустава, риск развития ПТОА колеблется от 20 до более чем 50 %. В последнее десятилетие активно обсуждается и изучается роль воспаления в развитии и прогрессировании ПТОА. Признаки воспаления можно наблюдать в суставных жидкостях и тканях у пациентов с травмой суставов и риском развития посттравматического остеоартрита. Кроме того, воспалительные механизмы способствуют риску развития остеоартрита и прогрессированию его после травмы. В развитии ПТОА задействованы молекулярные и клеточные механизмы. Синовиальная оболочка, суставной хрящ и субхондральная кость также реагируют на травму изменением метаболической активности и экспрессии провоспалительных белков. Данный обзор суммирует результаты недавних исследований патологических механизмов, лежащих в основе развития ПТОА. Это позволяет по-новому взглянуть на механизмы развития ПТОА, роль воспаления в прогрессировании болезни, а также оценить потенциальные возможности для раннего фармакологического вмешательства., Посттравматичний остеоартрит (ПТОА) виникає при травмі суглобів, на його частку припадає значна частина пацієнтів з остеоартритом (ОА). Внутрішньосуглобові переломи, що супроводжуються гемартрозом, розриви і грубі ушкодження менісків, зв’язкового апарату, травми хрящової тканини є найбільш частими причинами, що призводять до ПТОА. Пошкодження суглобового хряща може відбуватися в період відразу після травми, найближчим часом або розвиватися через кілька років після травми. Навіть при відповідному лікуванні, такому, як жорстка фіксація внутрішньосуглобових переломів, реконструкція пошкоджених зв’язок з успішним відновленням біомеханіки суглоба, ризик розвитку ПТОА коливається від 20 до більш ніж 50 %. Останнім десятиліттям активно обговорюється і вивчається роль запалення в розвитку і прогресуванні ПТОА. Ознаки запалення можна спостерігати в суглобових рідинах і тканинах у пацієнтів із травмою суглобів і ризиком розвитку посттравматичного остеоартриту. Крім того, запальні механізми сприяють ризику розвитку остеоартриту і прогресуванню його після травми. У розвитку ПТОА задіяні молекулярні і клітинні механізми. Синовіальна оболонка, суглобовий хрящ і субхондральна кістка також реагують на травму зміною метаболічної активності та експресії прозапальних білків. Даний огляд підсумовує результати недавніх досліджень патологічних механізмів, що лежать в основі розвитку ПТОА. Це дозволяє по-новому поглянути на механізми розвитку ПТОА, роль запалення в прогресуванні хвороби, а також оцінити потенційні можливості для раннього фармакологічного втручання.

The aim of the work was to evaluate the clinical and pathogenetic links of osteoarthritis (OA) with the qualitative composition of the drinking water in zones of patients’ residence. Material and Methods. The observation included 133 patients with primary OA aged 58.90 ± 0.83 years. In 33 urban and rural regions we have assessed levels of hardness and salinity of drinking water, concentration of chlorides, sulfates in it, phosphates and nitrates, content of toxic trace elements (Ba, Li, Ni, Pb). Results. Poor quality of drinking water in the regions where people live lead to the development of OA at a younger age, which subsequently determines the cumulative severity of articular syndrome, the nature of bone-destructive changes in the joints (osteoporosis, bone erosion, cartilage flaps), the formation of symptomatic reactive synovitis (chloride and nitrates concentration), the rate of disease progression, the emergence of intraarticular calcification deposits, osteophytosis and epiphyseal osteoporosis (degree of water salinity and hardness). The severity of OA and the rate of progression of bone-destructive changes in the joints depend on the level of trace elements, which determine the prevalence of joint syndrome, the development of Heberden’s and Bouchard’s nodes, spondylopathy, degree of reactive synovitis, osteoporosis, subchondral sclerosis, ligamentosis, intraarticular cartilage flaps and Hoffa’s bodies, and high content of Pb is a risk factor for unfavorable course of the disease. Conclusions. There were identified certain clinical and pathogenetic correlation of OA and the qualitative composition of drinking water in the regions where people live., Целью работы стала оценка клинико-патогенетических связей остеоартроза (ОА) с качественным составом питьевой воды в зонах проживания больных. Материал и методы. Под наблюдением находились 133 больных первичным ОA в возрасте 58,90 ± 0,83 года. Оценивали в 33 городских и сельских регионах уровни жесткости и минерализации питьевой воды, концентрации в ней хлоридов, сульфатов, фосфатов и нитратов, содержание токсичных микроэлементов (Ba, Li, Ni, Pb). Результаты. Низкое качество питьевой воды в регионах проживания людей способствует развитию ОА в более молодом возрасте, что в последующем определяет интегральную тяжесть артикулярного синдрома, характер костно-деструктивных изменений в суставах (развитие остеопороза, остеоузур, хондромных тел), формирование манифестного реактивного синовита (концентрации хлоридов и нитратов), темпы прогрессирования заболевания, появление внутрисуставных отложений кальцинатов, остеофитоза и эпифизарного остеопороза (степень минерализации и жесткости воды). Тяжесть ОА и темпы прогрессирования костно-деструктивных изменений со стороны суставов зависят от уровня микроэлементов, которые определяют распространенность суставного синдрома, развитие узелков Гебердена и/или Бушара, спондилопатии, степень реактивного синовита, остеопороза, субхондрального склероза, лигаментоза, интраартикулярных хондромных тел и тел Гоффа, а высокое содержание Pb является фактором риска неблагоприятного течения заболевания. Выводы: выявлены определенные клинико-патогенетические связи ОА с качественным составом питьевой воды в регионах проживания больных., Метою роботи стала оцінка клініко-патогенетичних зв’язків остеоартрозу (ОА) з якісним складом питної води в зонах проживання хворих. Матеріал і методи. Під спостереженням перебували 133 хворі на первинний ОA віком 58,90 ± 0,83 року. Оцінювали в 33 міських і сільських регіонах рівні жорсткості й мінералізації питної води, концентрації в ній хлоридів, сульфатів, фосфатів і нітратів, вміст токсичних мікроелементів (Ba, Li, Ni, Pb). Результати. Низька якість питної води в регіонах проживання людей сприяє розвитку ОА в молодшому віці, що в подальшому визначає інтегральну тяжкість артикулярного синдрому, характер кістково-деструктивних змін у суглобах (розвиток остеопорозу, остеоузур, хондромних тіл), формування маніфестного реактивного синовіту (концентрації хлоридів і нітратів), темпи прогресування захворювання, появу внутрішньосуглобових відкладень кальцинатів, остеофітозу й епіфізарного остеопорозу (ступінь мінералізації та жорсткості води). Тяжкість ОА і темпи прогресування кістково-деструктивних змін з боку суглобів залежать від рівня мікроелементів, які визначають поширеність суглобового синдрому, розвиток вузликів Гебердена та/або Бушара, спондилопатії, ступінь реактивного синовіту, остеопорозу, субхондрального склерозу, лігаментозу, інтраартикулярних хондромних тіл та тіл Гоффа, а високий вміст Pb є чинником ризику несприятливого перебігу захворювання. Висновки: виявлені певні клініко-патогенетичні зв’язки ОА з якісним складом питної води в регіонах проживання хворих.

Objective: Based on the expression changes in the TGF-β/ALK5/Smad2/3 signal transduction pathway, the repair of cartilage injury in the rabbit knee joint was investigated and evaluated by oral administration of naringin in combination with acellular dermal matrix implantation. Methods: First, twenty New Zealand white rabbits were randomly divided into five groups: a sham operation group (Sham group), a model group (Mod group), a naringin group (Nar group), an acellular dermal matrix group (ADM group), a naringin ​+ ​acellular dermal matrix group (Nar/ADM group). After the 12th week, the repaired tissues were assessed for histomorphology and repair content of the repaired site by observing the morphological characteristics of articular cartilage. The International Cartilage Repair Society (ICRS)'s macroscopic evaluation of the cartilage repair scale and the quantitative scoring repair effect of the modified O'Driscoll grading system were used as evaluation criteria. In addition, the structure of the rabbit knee joint was evaluated by micro-CT scan, histological staining (H & E staining, Alcian blue staining, Safranin-O staining) and immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining). Results: ① The observation of the repair morphology of joint defect tissues showed that the repair effects of the Nar and ADM groups were better than that of the Mod group, and the repair effect of Nar/ADM group was the best (P

Osteoarthritis (OA) is one of the most prevalent disorders in today's society, resulting in significant socio-economic costs and morbidity. MRI is widely used as a non-invasive imaging tool for OA of the knee. However, conventional knee MRI has limitations to detect subtle early cartilage degeneration before morphological changes are visually apparent. Novel MRI pulse sequences for cartilage assessment have recently received increased attention due to newly developed compositional MRI techniques, including: T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), sodium MRI, diffusion-weighted imaging (DWI)/ diffusion tensor imaging (DTI), ultrashort TE (uTE), and glycosaminoglycan specific chemical exchange saturation transfer (gagCEST) imaging. In this article, we will first review these quantitative assessments. Then, we will discuss the variations of quantitative values of knee articular cartilage with cartilage layer (depth)- and angle (regional)-dependent approaches. Multiple MRI sequence techniques can discern qualitative differences in knee cartilage. Normal articular hyaline cartilage has a zonal variation in T2 relaxation times with increasing T2 values from the subchondral bone to the articular surface. T1rho values were also higher in the superficial layer than in the deep layer in most locations in the medial and lateral femoral condyles, including the weight-bearing portion. Magic angle effect on T2 mapping is clearly observed in the both medial and lateral femoral condyles, especially within the deep layers. One of the limitations for clinical use of these compositional assessments is a long scan time. Recent new approaches with compressed sensing (CS) and MR fingerprinting (MRF) have potential to provide accurate and fast quantitative cartilage assessments.

BACKGROUND CONTEXT Low back pain is one of the most common musculoskeletal disorders. Although, the pathology of intervertebral disc (IVD) degeneration has been modeled using various biological methods, these models are inadequate for simulating similar pathologic states in humans. PURPOSE This study investigated whether monosodium iodoacetate (MIA) injection into the IVD of rats could generate a reliable model of IVD degeneration. STUDY DESIGN/SETTINGS In vivo animal study. METHODS MIA was injected into two-disc spaces (L4-5 and L5-6) of Sprague–Dawley rats. Their behaviors were examined by measuring weight load shifts from hind to forefoot, rearing, and von Frey tests. We examined the inhibition of pain behavior through intraperitoneal morphine injection and measured cyclooxygenase-2 (COX-2) and transcription factor nuclear factor-kappa B (NF-κB) levels in the IVD and dorsal root ganglion (DRG) by Western blot. Bone alterations were assessed by microfocus computed tomography (micro-CT), and IVD and/or cartilage changes were evaluated by hematoxylin and eosin and safranin-O staining and inducible nitric oxide synthase (iNOS) immunohistochemistry. The other authors declare no conflicts of interest. This project funded by the Memorial Fund and the National Research Foundation of Korea (NRF). RESULTS We observed increased weight load shifts to the forefoot and decreased rearing. Morphine-injected rats showed reduced pain. NF-κB and COX-2 expression increased in the IVD and left and/or right DRG. Micro-CT analyses suggested progressive bone deformation. Histologic examination showed decreased IVD width and nucleus pulposus area. Cartilaginous changes indicated epiphyseal growth plate loss. Finally, iNOS expression was increased in the subchondral endplate. CONCLUSIONS These results suggest that low back pain (LBP) models can be developed by MIA injection into the IVDs of rats and that an animal model is useful for exploring degenerative alterations in the affected discs. Therefore, MIA injection may be a useful model for the study of changes in the IVD to elucidate the mechanisms underlying clinical symptoms, such as LBP, in patients with IVD degeneration. CLINICAL SIGNIFICANCE This model in which MIA was injected into the disc better represented the human histologic and behavioral characteristics than the existing puncture model.

Polyvinyl alcohol hydrogel synthetic cartilage implants are increasingly used to treat advanced Freiberg disease. We report a case with recurrence of symptoms within 6 weeks and required revision for fracture of the implant. We describe a revision technique with modified osteochondral bone graft to deal with the variables of revision surgery namely: the bone loss, collateral ligament insufficiency, and changes to the proximal phalanx articular surface. We describe a postoperative plan, recovery and a good outcome achieved in 12 month follow-up.

Summary Objective There is a need to incorporate multiple tissues into in vitro OA models to evaluate novel therapeutics. This approach is limited by inherent donor variability. We present an optimized research tool: a human OA cartilage-synovium explant co-culture model (OA-EXM) that employs donor-matched lower and upper limit response controls combined with statistical approaches to address variability. Multiple rapid read-outs allow for evaluation of therapeutics while cataloguing cartilage-synovium interactions. Design 48-h human explant cultures were sourced from OA knee arthroplasties. An OA-like cartilage-synovium co-culture baseline was established relative to donor-matched upper limit supraphysiological pro-inflammatory cytokine and lower limit OA cartilage or synovium alone controls. 100 nM dexamethasone treatment validated possible “rescue effects” within the OA-EXM dual tissue environment. Gene expression, proteoglycan loss, MMP activity, and soluble protein concentrations were analyzed using blocking and clustering methods. Results The OA-EXM demonstrates the value of the co-culture approach as the addition of OA synovium increases OA cartilage proteoglycan loss and expression of MMP1, MMP3, MMP13, CXCL8, CCL2, IL6, and PTGS2, but not to the extent of supraphysiological stimulation. Conversely, OA cartilage does not affect gene expression or MMP activity of OA synovium. Dexamethasone shows dual treatment effects on synovium (pro-resolving macrophage upregulation, protease downregulation) and cartilage (pro-inflammatory, catabolic, and anabolic downregulation), and decreases soluble CCL2 levels in co-culture, thereby validating OA-EXM utility. Conclusions The OA-EXM is representative of late-stage OA pathology, captures dual interactions between cartilage and synovium, and combined with statistical strategies provides a rapid, sensitive research tool for evaluating OA therapeutics.

Arthritis and osteoporosis are two common disorders in the world, especially for the elder, but the current treatments have limited efficacy. Herein, we aimed to determine whether the novel technique, neurological training can alleviate osteoporosis complicated with arthritis in rat model. Thirty rats were assigned into normal group, model group, and treatment group (treated with forsythin and neurological training) (n = 10) followed by assessment of chondrocytes and osteoblasts using Mankin score, apoptosis by TUNEL and flow cytometry, and IL-1β, TNF-α, and Aggrecan levels. Apoptotic chondrocytes of treatment group (27.43±1.34) was lower than model group (p < 0.05), whereas amount of osteoblast was increased upon forsythin and neurological training, with lower Mankin’s score (6.38±0.76). Besides, the content of IL-1β and TNF-α of treatment group was significantly lower but Aggrecan mRNA and protein expression was significantly higher. In conclusion, neurological training could protect and alleviate osteoporosis complicated with arthritis.

Graphical abstract, Highlights • Established a new experimental rat model of the developmental trochlear dysplasia; • Using the macroscopic morphological and micro-CT to assess trochlear dysplasia; • Using Histological staining to investigate the cartilage degradation of the model; • Investigated the relationship of the PI3K/AKT signaling pathway with trochlear dysplasia cartilage degeneration; • Using immunohistochemistry and qPCR to investigate the PI3K/AKT and the marker of the cartilage degeneration., Introduction Trochlear dysplasia is a commonly encountered lower extremity deformity in humans. However, the molecular mechanism of cartilage degeneration in trochlear dysplasia is unclear thus far. Objectives The PI3K/AKT signaling pathway is known to be important for regulating the pathophysiology of cartilage degeneration. The aim of this study was to investigate the relationship of the PI3K/AKT signaling pathway with trochlear dysplasia cartilage degeneration. Methods In total, 120 female Sprague-Dawley rats (4 weeks of age) were randomly separated into control and experimental groups. Distal femurs were isolated from the experimental group at 4, 8, and 12 weeks after surgery; they were isolated from the control group at the same time points. Micro-computed tomography and histological examination were performed to investigate trochlear anatomy and changes in trochlear cartilage. Subsequently, expression patterns of PI3K/AKT, TGFβ1, and ADAMTS-4 in cartilage were investigated by immunohistochemistry and quantitative polymerase chain reaction. Results In the experimental group, the trochlear dysplasia model was successfully established at 8 weeks after surgery. Moreover, cartilage degeneration was observed beginning at 8 weeks after surgery, with higher protein and mRNA expression levels of PI3K/AKT, TGFβ1, and ADAMTS-4, relative to the control group. Conclusion Patellar instability might lead to trochlear dysplasia in growing rats. Moreover, trochlear dysplasia may cause patellofemoral osteoarthritis; cartilage degeneration in trochlear dysplasia might be associated with activation of the PI3K/AKT signaling pathway. These results provide insights regarding the high incidence of osteoarthritis in patients with trochlear dysplasia. However, more research is needed to clarify the underlying mechanisms.

Summary Background With the experience-based hypothesis of low donor site morbidity (DSM) for free flaps from the distal femur, this cohort study aimed to evaluate the DSM according to objective and reproducible criteria. Methods One hundred and fifty-six patients who had a flap harvest from either the medial or lateral femoral condyle region between 2005 and 2017 were included. A retrospective chart review was performed for all patients. In total, 97 patients were available for a follow-up examination. Outcomes were assessed according to objective (Knee Society Score; Larson Knee Score; OAK Score; 0–100 points), patient-reported (IKDC Score; KOOS Score; 0–100 points), and radiologic criteria (Kellgren and Lawrence Score; MRI Osteoarthritis Knee Score). Results The median follow-up time was 1,529 days (range: 248–4,810). The mean Knee Society Score (94.8 ± 10.1), Larson Knee Score (94.5 ± 10.1), and OAK Score (95.5 ± 6.6) showed nearly unimpaired knee function. The overall patient-reported DSM was low (IKDC Score: 86.7 ± 17.4; KOOS Score: 89.3 ± 17.1). Osteochondral (OC) flaps had a significantly higher DSM, regardless of the donor site. Bone flaps did not show any relevant radiologic morbidity in the Kellgren and Lawrence Score. Besides the procedure-associated cartilage lesions at the OC donor sites, MRI Osteoarthritis Knee Score did not show any significant presence of further knee pathologies in the bilateral MRI Scans. The obvious cartilage lesions did not have a relevant impact on the knee function of most patients. Conclusion The DSM for bone and soft-tissue flaps from the femoral condyle region is negligible. OC flaps are associated with a significantly higher DSM, although a clinically relevant impact on knee function was not evident in the majority of patients.

Segmentation of knee articular cartilage tissue (ACT) from 3D magnetic resonance images (MRIs) is a fundamental task in assessing knee osteoarthritis (KOA). However, automated ACT segmentation of knee cartilage is complicated by (1) the variability of pathological structures in terms of shape, size, spatial resolution and (2) the uncertainties in delineating inter- and intra-cartilage boundaries (possibly touching inter-cartilage surfaces, intensity inhomogeneity, cartilage loss due to disease progression). To address these problems, we propose a novel joint deep and hand-crafted learning-based (JD-HCl) framework. The fully automated segmentation pipeline is a combination of three main steps: 3D convolutional neural networks (CNNs), diffeomorphic mapping, and a conventional hand-crafted feature-based classification model. Firstly, the initial segmentation of knee ACT was drawn from preprocessed knee MRIs using 3D U-Net. Secondly, the spatial alignment in the image domain was carried out using diffeomorphic image registration derived from an estimate of the anatomical correspondences between the subjects and population-specific template. Finally, a tissue-specific hand-crafted feature set was extracted from the spatially aligned pre-segmented ACT region and combined with the semantic context priors obtained from 3D CNN model to develop the second-stage learning model. The proposed method was evaluated with two publicly available Osteoarthritis Initiative (OAI) datasets and one in-house MRI sequences from the Alfred hospital, Melbourne, Australia. The proposed JD-HCl framework produced strong Dice similarity coefficient (DSC), ranging between 97.4% and 98.5% (95% confidence interval) for all cartilage compartments at baseline to 97.2% and 98.5% (the 1-year follow-up) for OAI(-Imorphics) dataset, and 89.3% and 94.6% for OAI-ZIB validation dataset, respectively. Average correlations of cartilage volumes between manual and automatic segmentations were 0.9 and 0.83 for OAI-ZIB dataset, respectively, and 0.975, 0.995, and 0.99 for OAI(-Imorphics) validation datasets, respectively. In longitudinal studies, accurate segmentation of knee ACT using the proposed method produces reproducible cartilage volume, thickness measurements valuable for the study of KOA progression.

Osteoarthritis (OA) is characterized by the gradual loss of cartilage. Sprifermin, a recombinant FGF18, is being developed as a cartilage anabolic drug. PRO-C2 is a serum marker of type II collagen formation and low levels have been shown to be prognostic of radiographic progression. The aim of the study was to investigate whether the patient groups with either high or low PRO-C2 levels responded differently to sprifermin.PRO-C2 was measured in synovial fluid (SF) (n = 59) and serum samples (n = 225) from participants of the FORWARD study, a 2-year phase IIb clinical trial testing the efficacy of intra-articular (IA) sprifermin over placebo. The difference between sprifermin and placebo in respect to in change cartilage thickness (measured by quantitative (q) MRI) was analyzed in groups with either high or low (3SF levels of PRO-C2 increased over time in response to sprifermin, but not to placebo. In the placebo arm, significantly (p = 0.005) more cartilage was lost in the low vs high PRO-C2 group over the 2-year period. The contrast between sprifermin and placebo was significant (p 0.001), ranging from 0.104 mm at week 26 to 0.229 mm at week 104 in the low PRO-C2 group. This result was not significant in the high PRO-C2 group ranging from -0.034 to 0.142.Patients with low serum PRO-C2 levels lost more cartilage thickness over time and grew more cartilage in response to sprifermin vs a placebo when compared to patients with high PRO-C2 levels.

The complex framework of the human nasal cartilages is unique among mammals. It is the mobile portal to the respiratory system providing conditions for the passage of airstreams and for the generation of nasal resistance and turbulence. Already in utero, the septodorsal (septolateral) cartilage develops as the dominating structure for nasal and midfacial growth. This is briefly shown in Sect. 34.1. The dominating role of this cartilage for the nasal appearance and for nasal physiology and pathophysiology is preserved lifelong. Together with the erectile lining of the nasal cavities, the cartilaginous framework enables air-conditioning and the acting of the nasal cycle. The anterior nose with the nasal valve as its crucial region is the narrowest part of the upper airways and provides two-thirds of the total airway resistance. Due to its protruding exposition, it is especially vulnerable to external injuries and may react as a protecting crumpled zone. No wonder that most of the structures obstructing the nasal airways are diagnosed in the anterior nose. This is discussed in Sect. 34.2. In Sect. 34.3, clinical and histological examples are presented showing the long-term effects of the disturbed cartilaginous nasal framework caused by congenital and epigenetic factors such as hormones, infections and injuries including nasal surgery. In Sect. 34.4, some surgical procedures and their long-term results are discussed to restore the physiological functions of the anterior nose, the site of the most resistive nasal segments, where deformities of the cartilaginous skeleton predominantly obstruct the nasal airways.

The main indication for medial Unicondylar Knee Arthroplasty (UKA) is Full-Thickness Cartilage Loss (FTCL) in the isolated medial compartment of the knee. However, controversial outcomes were reported in patients with Partial-Thickness Cartilage Loss (PTCL). The aim of this study is to compare PTCL and FTCL based on intraoperative findings in medial UKA in terms of functional outcomes and complication rates requiring reoperation and revision.Two hundred and fifteen knees of 174 patients who underwent mobile-bearing UKA between October 2014 and February 2018 for the diagnosis of symptomatic anteromedial osteoarthritis were evaluated retrospectively. A single senior surgeon evaluated the type of cartilage loss in the medial compartment intraoperatively according to the International Cartilage Repair Society classification system. Clinical outcomes were evaluated using Oxford Knee Score (OKS) and International Knee Documentation Committee (IKDC) score pre- and post-operatively at the last follow-up. Patients with PTCL and FTCL were compared in terms of their pre- and post-operative OKS and IKDC scores, and their improvements, as well as complication rates requiring reoperation and revision.The mean follow-up time was 33.1 ± 5.3 months. The PTCL (n = 80) and FTCL (n = 135) groups were statistically similar in terms of age (P = 0.41), gender (P = 0.921), body mass index (P = 0.165), bilaterality (P = 0.111), American Society of Anesthesiologists physical status (P = 0.218), Charlson Comorbidity Index (P = 0.74), and post-operative follow-up (P = 0.167). The mean pre-operative OKS and IKDC scores were improved from 24.5 ± 4.1 and 39.9 ± 5 to 40.3 ± 3.6 and 73.9 ± 7.7 at the last follow-up, respectively (P0.001). Pre-operative OKS and IKDC scores were superior in favor of the PTCL group. However, no significant difference was found between the groups in terms of post-operative OKS (P = 0.53) and IKDC (P = 0.975) scores, and their improvements (OKS, P = 0.953; IKDC, P = 0.536). The complication rates requiring reoperation was 5% (n = 11) in all patients. Of these, 9% (n = 7) from the PTCL group and 3% (n = 4) from the FTCL group were reoperated. Nevertheless, no significant difference was found between the groups (P = 0.105).In PTCL, medial UKA is a reliable surgery in terms of functional outcomes, the same as in FTCL; however, its complication rates requiring reoperation is higher without statistical significance.Level III, Therapeutic Study.

Objective Mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO). Methods Ift88fl/fl and aggrecanCreERT2 mice were crossed to create a strain of cartilage-specific Ift88-KO mice (aggrecanCreERT2;Ift88fl/fl). In these Ift88-KO mice and Ift88fl/fl control mice, tibial articular cartilage thickness was assessed by histomorphometry, and the integrity of the cartilage was assessed using Osteoarthritis Research Society International (OARSI) damage scores, from adolescence through adulthood. In situ mechanisms of cartilage damage were investigated in the microdissected cartilage sections using immunohistochemistry, RNAScope analysis, and quantitative polymerase chain reaction. Osteoarthritis (OA) was induced in aggrecanCreERT2;Ift88fl/fl mice and Ift88fl/fl control mice using surgical destabilization of the medial meniscus (DMM). Following tamoxifen injection and DMM surgery, the mice were given free access to exercise on a wheel. Results Deletion of Ift88 resulted in progressive reduction in the thickness of the medial tibial cartilage in adolescent mice, as well as marked atrophy of the cartilage in mice during adulthood. In aggrecanCreERT2;Ift88fl/fl mice at age 34 weeks, the median thickness of the medial tibial cartilage was 89.42 μm (95% confidence interval [95% CI] 84.00–93.49), whereas in Ift88fl/fl controls at the same age, the median cartilage thickness was 104.00 μm (95% CI 100.30–110.50; P Conclusion Our results in a mouse model of OA demonstrate that IFT88 performs a chondroprotective role in articular cartilage by controlling the calcification of cartilage via maintenance of a threshold of Hh signaling during physiologic loading.

Purpose Several factors present at the time of posterior cruciate ligament reconstruction (PCLR) may cause the subsequent progression of articular cartilage lesions. This study aimed to evaluate postsurgical articular cartilage lesions which can be seen on MRI in patients who underwent arthroscopic PCLR with or without concomitant meniscal pathology. Material and methods A total of sixty-five patients (mean age 35.8 ± 12.3 years) who underwent arthroscopic PCLR were included in this retrospective study. Patients were divided into two groups: ten patients with concomitant meniscal injuries at the time of PCLR who underwent meniscal surgery and fifty-five patients with intact menisci. The cartilage status of all knees was evaluated by MRI and modified Noyes classification. Results Cartilage lesions were observed in 18 patients (27.7%) on the last follow-up MRI. The cartilage lesions were more common in the medial (15.4%) and patellofemoral (12.3%) compartments than in the lateral compartment (7.7%). Progression of cartilage lesions was present in 11 patients (16.9%) during follow-up MRI. The majority of cartilage lesions with progression were located in the medial compartment. The meniscal pathology group showed a higher prevalence of articular cartilage lesions on the last follow-up MRI (21.8% versus 60%, p = 0.022). In multivariate Cox regression, concomitant meniscal pathology was significantly associated with progression of articular cartilage lesions (p = 0.044). Conclusion PCLR patients with associated meniscal pathology showed worse cartilage condition and more progression of cartilage lesions than isolated PCLR patients. Attention to this risk factor might provide more applicable treatment options for potential osteoarthritis prevention strategies.

Summary Objective Biochemical joint changes contribute to posttraumatic osteoarthritis (PTOA) development following anterior cruciate ligament reconstruction (ACLR). The purpose of this longitudinal cohort study was to compare tibiofemoral cartilage composition between ACLR patients with different serum biochemical profiles. We hypothesized that profiles of increased inflammation (monocyte chemoattractant protein-1 [MCP-1]), type-II collagen turnover (type-II collagen breakdown [C2C]:synthesis [CPII]), matrix degradation (matrix metalloproteinase-3 [MMP-3] and cartilage oligomeric matrix protein [COMP]) preoperatively to 6-months post-ACLR would be associated with greater tibiofemoral cartilage T1ρ relaxation times 12-months post-ACLR. Design Serum was collected from 24 patients (46% female, 22.1 ± 4.2 years old, 24.0 ± 2.6 kg/m2 body mass index [BMI]) preoperatively (6.4 ± 3.6 days post injury) and 6-months post-ACLR. T1ρ Magnetic Resonance Imaging (MRI) was collected for medial and lateral tibiofemoral articular cartilage at 12-months post-ACLR. A k-means cluster analysis was used to identify profiles based on biomarker changes over time and T1ρ relaxation times were compared between cluster groups controlling for sex, age, BMI, concomitant injury (either meniscal or chondral pathology), and Marx Score. Results One cluster exhibited increases in MCP-1 and COMP while the other demonstrated decreases in MCP-1 and COMP preoperatively to 6-months post-ACLR. The cluster group with increases in MCP-1 and COMP demonstrated greater lateral tibial (adjusted mean difference = 3.88, 95% confidence intervals [1.97–5.78]) and femoral (adjusted mean difference = 12.71, 95% confidence intervals [0.41–23.81]) T1ρ relaxation times. Conclusion Profiles of increased serum levels of inflammation and matrix degradation markers preoperatively to 6-months post-ACLR are associated with MRI changes consistent with lesser lateral tibiofemoral cartilage proteoglycan density 12-months post-ACLR.

Background We evaluated the risk factors for pain catastrophizing, kinesiophobia, and elevated depressive symptoms among patients undergoing high-grade cartilage defect surgery. We hypothesized that cartilage patients would demonstrate high scores on pain catastrophizing, kinesiophobia, and depression testing prior to surgery. Methods Two hundred and ten patients undergoing surgery for high-grade cartilage defects (56% chondroplasty, 36% microfracture, 22% autologous chondrocyte implantation) completed a preoperative survey before undergoing surgery. Outcome scores assessed were: International Knee Documentation Committee-Symptom (IKDC-S) score, Tegner activity score, Pain catastrophizing scale (PCS), Tampa scale for kinesiophobia (TSK-11), and Patient Health Questionnaire depression scale (PHQ-9). Multivariate logistic regression was used to determine what pre-operative factors predicted pain catastrophizing, kinesiophobia, and elevated depressive symptoms. Results The mean pre-operative Tegner score was 5.8 (SD 2.4) and IKDC-S score was 44.7 (SD 11.1). Prior to surgery, 19% had abnormal pain catastrophizing (PCS ≥ 20 points), 14.4% had moderate-severe depression (PHQ ≥ 10), and 49.0% had high kinesiophobia (TSK-11 ≥ 25). Lower pre-operative Tegner scores predicted moderate-severe depressive symptoms (per point decrease, OR 1.36, 95% CI 1.06, 1.76; p = 0.008). Predictors of elevated pain catastrophizing were lower pre-operative IKDC-S scores (per 5-point decrease, OR 1.28, 95% CI 1.08, 1.51; p = 0.002) and symptom duration >6 months (OR 2.20 CI 1.14, 4.32; p = 0.02). A lower pre-operative IKDC-S score (per 5-point decrease, OR 1.17, CI 1.03, 1.33; p = 0.02) predicted elevated kinesiophobia. Conclusion Low self-reported function, low activity level and symptom duration greater than six months are associated with poor preoperative psychological status.

Objective The purpose of this study is to systematically review the literature and to evaluate the outcomes following bone marrow stimulation (BMS) for nonprimary osteochondral lesions of the talus (OLT). Design A literature search was performed to identify studies published using PubMed (MEDLINE), EMBASE, CDSR, DARE, and CENTRAL. The review was performed according to the PRISMA guidelines. Two authors separately and independently screened the search results and conducted the quality assessment using the Methodological Index for Non-Randomized Studies (MINORS). Studies were pooled on clinical, sports, work, and imaging outcomes, as well as revision rates and complications. The primary outcome was clinical success rate. Results Five studies with 70 patients were included in whom nonprimary OLTs were treated with secondary BMS. The pooled clinical success rate was 61% (95% confidence interval [CI], 50-72). The rate of return to any level of sport was 83% (95% CI, 70-91), while the return to pre-injury level of sport was 55% (95% CI, 34-74). The rate of return to work was 92% (95% CI, 78-97), and the complication rate was assessed to be 10% (95% CI, 4-22). Imaging outcomes were heterogeneous in outcome assessment, though a depressed subchondral bone plate was observed in 91% of the patients. The revision rate was 27% (95% CI, 18-40). Conclusions The overall success rate of arthroscopic BMS for nonprimary osteochondral lesions of the talus was 61%, including a revision rate of 27%. Return to sports, work, and complication outcomes yielded fair to good results.

Background and purpose of the study Arthroscopic debridement, the most commonly applied surgical technique for focal cartilage lesions in the knee, is not included in most treatment algorithms because of discouraging results in the management of osteoarthritis of the knee. The present systematic review evaluates the outcome of arthroscopic cartilage debridement as the primary treatment of focal knee chondral lesions in adults, and defines its indications and role as the primary treatment of focal knee chondral lesions. Methods Two independent investigators searched PubMed, Cochrane CENTRAL, and Virtual Health Library databases using the terms “knee”, “cartilage”, “chondral”, “lesions”, “injury”, “damage”, “debridement”, “chondroplasty”, “chondrectomy”, alone and in combination. Clinical studies evaluating the effect of mechanical cartilage debridement in adults with symptomatic focal cartilage lesions in the knee joint regardless of the defect size and depth were included. We excluded studies if patients had a concomitant ligament or meniscus injury, and/or had additional debridement with monopolar radiofrequency energy. Main findings Available studies suggest good to excellent short and medium-term functional outcomes (KOOS, LKSS, Tegner scale) for focal cartilage lesions treated with debridement regardless of the defect size and depth. Data are lacking comparing cartilage debridement versus other cartilage repair techniques. Conclusions Arthroscopic debridement of focal articular cartilage lesions of the knee is associated with good to excellent short and medium-term postoperative outcomes, especially in terms of functional improvement. Arthroscopic debridement may be considered in the primary treatment of focal cartilage injuries regardless of the defect size and depth. However, available studies are limited and the level of evidence is low.

Chondrosarcomas are heterogeneous matrix-producing cartilaginous neoplasms with variable clinical behavior. Subtypes include conventional (75%), dedifferentiated (10%), clear cell (2%), mesenchymal (2%), and periosteal chondrosarcoma (