Search

Objective: A complex association exists between aberrant gait biomechanics and posttraumatic knee osteoarthritis (PTOA) development. Previous research has primarily focused on the link between peak loading during the loading phase of stance and joint tissue changes following anterior cruciate ligament reconstruction (ACLR). However, the associations between loading and cartilage composition at other portions of stance, including midstance and late stance, is unclear. The objective of this study was to explore associations between vertical ground reaction force (vGRF) at each 1% increment of stance phase and tibiofemoral articular cartilage magnetic resonance imaging (MRI) T1ρ relaxation times following ACLR., Design: Twenty-three individuals (47.82% female, 22.1 ±4.1 years old) with unilateral ACLR participated in a gait assessment and T1ρ MRI collection at 12.25 ± 0.61 months post-ACLR. T1ρ relaxation times were calculated for the articular cartilage of the weightbearing medial and lateral femoral (MFC, LFC) and tibial (MTC, LTC) condyles. Separate bivariate, Pearson product moment correlation coefficients ( r ) were used to estimate strength of associations between T1ρ MRI relaxation times in the medial and lateral tibiofemoral articular cartilage with vGRF across the entire stance phase., Results: Greater vGRF during midstance (46%-56% of stance phase) was associated with greater T1ρ MRI relaxation times in the MFC ( r ranging between 0.43 and 0.46)., Conclusions: Biomechanical gait profiles that include greater vGRF during midstance are associated with MRI estimates of lesser proteoglycan density in the MFC. Inability to unload the ACLR limb during midstance may be linked to joint tissue changes associated with PTOA development.

Objective: The primary aim was to determine differences in talocrural and subtalar joint (STJ) articular cartilage composition, using T1ρ magnetic resonance imaging (MRI) relaxation times, between limbs in individuals with unilateral chronic ankle instability (CAI) and compare with an uninjured control. Our secondary purpose was to determine the association between talocrural and STJ composition in limbs with and without CAI., Design: T1ρ MRI relaxation times were collected on 15 CAI (11 females, 21.13 ± 1.81 years, body mass index [BMI] = 23.96 ± 2.74 kg/m 2 ) and 15 uninjured control individuals (11 females, 21.07 ± 2.55 years, BMI = 24.59 ± 3.44 kg/m 2 ). Talocrural cartilage was segmented manually to identify the overall talar dome. The SJT cartilage was segmented manually to identify the anterior, medial, and posterior regions of interest consistent with STJ anatomical articulations. For each segmented area, a T1ρ relaxation time mean and variability value was calculated. Greater T1ρ relaxation times were interpreted as decreased proteoglycan content., Results: Individuals with CAI demonstrated a higher involved limb talocrural T1ρ mean and variability relative to their contralateral limb ( P < 0.05) and the healthy control limb ( P < 0.05). The CAI-involved limb also had a higher posterior STJ T1ρ mean relative to the healthy control limb ( P < 0.05). In healthy controls ( P < 0.05), but not the CAI-involved or contralateral limbs (p>0.05), talocrural and posterior STJ composition measures were positively associated., Conclusions: Individuals with CAI have lower proteoglycan content in both the talocrural and posterior STJ in their involved limbs relative to the contralateral and a healthy control limb. Cartilage composition findings may be consistent with the early development of posttraumatic osteoarthritis.

Objective: The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression., Design: Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages., Results: We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules- Gnai1, Sema4d, Plxnb1 , and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining., Conclusions: Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.

Objective: To delineate the response of migrating chondrogenic progenitor cells (CPCs) that arose from the surface of mechanically injured articular cartilage to proinflammatory damage-associated-molecular-patterns (DAMPs)., Design: Bovine CPCs and non-CPC chondrocytes isolated from either impacted or scratched articular cartilage were studied. Those 2 types of cells were treated with mitochondrial DAMPs (MTDs; 10 nM fMLF and 10 µg/mL CpG DNA), or 10 nM HMGB1, or 10 ng/mL IL-1b for 24 hours. At the end of experiments, conditioned media and cell lysates were collected for analysis of expression levels of matrix metalloproteinases (MMPs), chemokines, and cytokines that are associated with cartilage degeneration with Western blotting and quantitative polymerase chain reaction. The difference of expression levels was compared by Welch's t -test., Results: Our data indicated that HMGB1 and MTDs remarkably upregulated pro-MMP-13 expression in CPCs. Compared with non-CPCs, CPCs expressed significantly more baseline mRNAs of MMP-13, CXCL12, and IL-6. MTDs greatly increased the expression of MMP-13 and IL-6 in CPCs by over 100-fold ( P < 0.001). MTDs also significantly increased IL-8 expression in CPCs to a similar extent ( P < 0.001). However, when IL-1b was present, CPCs expressed less MMP-3 and active MMP-13 proteins as well as less CCL2 and IL-6 than did non-CPCs., Conclusions: We concluded that CPCs were more sensitive than non-CPCs in response to DAMPs, especially MTDs. The proinflammatory nature of CPCs implied their critical role in the early phase of posttraumatic osteoarthritis development.

Objective: To evaluate the effect of intra-articular injection of autologous micronized adipose tissue (MAT) with ankle arthroscopic debridement in patients with advanced-stage posttraumatic osteoarthritis (PTOA) of ankle., Design: A retrospective cohort study investigating patients treated with arthroscopic debridement and autologous MAT injection for ankle PTOA was performed. Patients with Kellgren-Lawrence (KL) grade 3 to 4 were included. Visual analogue scale (VAS), Foot and Ankle Outcome Scores (FAOS), and patient satisfaction were evaluated., Results: A total of 19 patients (19 ankles) were included (KL grade 3, 8 patients; grade 4, 11 patients). At a mean follow-up time of 14.3 months (range, 7-23 months), the mean FAOS subscales for pain and quality of life significantly increased from 48.8 and 20.1 preoperatively to 61.1 and 30.1 ( P = 0.029 and 0.048, respectively). The mean VAS score significantly improved from 6.1 to 3.8 (P = 0.003) at final follow-up. A total of 10.5% (2/19) of patients were very satisfied, 31.6% (6/19) satisfied, 26.3% (5/19) neutral, 21.1% (4/19) unsatisfied, and 10.5% (2/19) very unsatisfied with their outcomes. The overall FAOS score demonstrated a significant difference in pre- to postoperative change with 14.8 for KL grade 3 and 5.9 for KL grade 4 ( P = 0.048)., Conclusions: Autologous MAT injection is a safe and potentially beneficial procedure for advanced-stage ankle PTOA as an adjunct to arthroscopic debridement, although more than one-third of patients were unsatisfied with the procedure. This procedure may be more beneficial for KL grade 3 patients than grade 4 patients. However, future investigations are necessary to define the role of MAT for ankle PTOA.

The knee joint is one of the most frequently injured joints in the body, and the resulting injury may often lead to the presence of a bloody effusion, or hemarthrosis. The acute management of this condition can have long-lasting implications, and may ultimately result in the early onset of osteoarthritis in this population. Heme, a breakdown product of erythrocytes, and associated pro-inflammatory mediators, are known to have deleterious interactions with cartilage and synovium. The presence of blood in a joint following injury can precipitate these effects and accelerate the degenerative changes in the joint. Currently, there is no consensus on the optimal management of a traumatic knee joint injury with a hemarthrosis. Nontraumatic hemarthosis, seen most commonly in hemophilia patients, has a set of established guidelines that does not routinely recommend drainage of the joint. This article presents a rationale for joint aspiration to minimize the harmful effects of blood following traumatic hemarthrosis.

Objectives: Osteoarthritis is a painful joint disease responsible for walking impairment. Its quantitative assessment by gait analysis in mice may be a relevant and noninvasive strategy to assess the disease severity. In this study, we aimed to determine the severity of osteoarthritis at the tissular and gait levels in unilateral and bilateral posttraumatic murine osteoarthritis., Methods: Twenty-four C57BL/6 male mice were randomly assigned to 3 groups ( n = 8/group): controls, unilateral surgery, and bilateral surgery. Posttraumatic osteoarthritis was induced unilaterally or bilaterally by destabilization of the medial meniscus. Gait analysis was performed weekly with the CatWalk TM XT system until the 16th week after surgery. After animal sacrifices, histological and micro-computed tomographic assessment was performed., Results: Operated knees showed a significant increase in the histological score compared with controls ( P < 0.001). Calcified anterior medial meniscal bone volume was higher on the ipsilateral side after unilateral destabilization of the medial meniscus ( P < 0.001) and on both sides after bilateral intervention ( P < 0.01). One week after surgery, the mice mean speed decreased significantly in both operated groups ( P < 0.001 and P < 0.05). In the unilateral group, a significant increase in the contralateral hind print area appeared from week 4 to week 16., Conclusions: While bilateral destabilization of the medial meniscus induced no detectable gait modification except 1 week after surgery, unilateral model was responsible for a gait disturbance on the contralateral side. Further studies are needed to better define the place of the CatWalk TM in the evaluation of mouse models of osteoarthritis.

Objective: Excessive articular loading, for example, an ankle sprain, may result in focal osteochondral damage, initiating a vicious degenerative process resulting in posttraumatic osteoarthritis (PTOA). Better understanding of this degenerative process would allow improving posttraumatic care with the aim to prevent PTOA. The primary objective of this study was to establish a drop-weight impact testing model with controllable, reproducible and quantitative axial impact loads to induce osteochondral damage in caprine tibiotalar joints. We aimed to induce osteochondral damage on microscale level of the tibiotalar joint without gross intra-articular fractures of the tibial plafond., Design: Fresh-frozen tibiotalar joints of mature goats were used as ex vivo articulating joint models. Specimens were axially impacted by a mass of 10.5 kg dropped from a height of 0.3 m, resulting in a speed of 2.4 m/s, an impact energy of 31.1 J and an impact impulse of 25.6 N·s. Potential osteochondral damage of the caprine tibiotalar joints was assessed using contrast-enhanced high-resolution micro-computed tomography (micro-CT). Subsequently, we performed quasi-static loading experiments to determine postimpact mechanical behavior of the tibiotalar joints., Results: Single axial impact loads with a mass of 15.5 kg dropped from 0.3 m, resulted in intra-articular fractures of the tibial plafond, where a mass of 10.55 kg dropped from 0.3 m did not result in any macroscopic damage. In addition, contrast-enhanced high-resolution micro-CT imaging neither reveal any acute microdamage (i.e., microcracks) of the subchondral bone nor any (micro)structural changes in articular cartilage. The Hexabrix content or voxel density (i.e., proteoglycan content of the articular cartilage) on micro-CT did not show any differences between intact and impacted specimens. However, quasi-static whole-tibiotalar-joint loading showed an altered biomechanical behavior after application of a single axial impact (i.e., increased hysteresis when compared with the intact or nonimpacted specimens)., Conclusions: Single axial impact loads did not induce osteochondral damage visible with high-resolution contrast-enhanced micro-CT. However, despite the lack of damage on macro- and even microscale, the single axial impact loads resulted in "invisible injuries" because of the observed changes in the whole-joint biomechanics of the caprine tibiotalar joints. Future research must focus on diagnostic tools for the detection of early changes in articular cartilage after a traumatic impact (i.e., ankle sprains or ankle fractures), as it is well known that this could result in PTOA.

Objective Early intervention therapies targeting inflammation and cell death during the acute phase of cartilage injury have the potential to prevent posttraumatic osteoarthritis. The objective of this study was to investigate the effects of interleukin receptor antagonist protein (IRAP), hyaluronan (HA), dexamethasone (DEX), and mesenchymal stem cell (MSC) treatment on the expression of established genetic markers for matrix degradation, apoptosis, and inflammation in articular cartilage during the acute phase of injury. Design A custom impact device was used to create replicable injury ex vivo to intact porcine knee joint. One hour after impact, IRAP, HA, DEX, or MSCs was intra-articularly injected. At 8 hours postinjury, cartilage and meniscus samples were harvested for genetic expression analysis. Expression of miR-27b, miR-140, miR-125b, miR-16, miR-34a, miR-146a, miR-22, ADAMTS-4, ADAMTS-5, MMP-3, IL-1β, and TNF-α was analyzed by real-time polymerase chain reaction. Results At 8 hours postinjury, expression of ADAMTS-4, ADAMTS-5, MMP-3, IL-1β, and TNF-α in cartilage was significantly decreased in IRAP- and DEX-treated joints as compared to nontreated injured joints, whereas only IRAP upregulated expression of miR-140, miR-125b, miR-27b, miR-146a, and miR-22 in cartilage. HA and MSC treatments had no significant effects on catabolic and inflammatory gene expression in cartilage. However, HA treatment significantly upregulated expression of all miRNAs except miR-16. In addition, the treatments tested also exhibited significant influences on meniscus. Conclusions This study provides a valuable starting point for further research into potential targets for and efficacy of various early intervention strategies that may delay or prevent the progression of posttraumatic osteoarthritis after acute cartilage injury.

Posttraumatic osteoarthritis (PTOA) is the most common form of osteoarthritis (OA) of the ankle joint. PTOA occurs as a result of several factors, including the poor regenerative capacity of hyaline articular cartilage as well as increased contact stresses following trauma. The purpose of this article is to review the epidemiology, pathogenesis, and potential targets for treatment of PTOA in the ankle joint. Previous reviews primarily addressed clinical approaches to ankle PTOA, while the focus of the current article will be specifically on the newly acquired knowledge of the cellular mechanisms that drive PTOA in the ankle joint and means for potential targeted therapeutics that might halt the progression of cartilage degeneration and/or improve the outcome of surgical interventions. Three experimental treatment strategies are discussed in this review: (1) increasing the anabolic potential of chondrocytes through treatment with growth factors such as bone morphogenetic protein-7; (2) limiting chondrocyte cell death either through the protection of cell membrane with poloxamer 188 or inhibiting activity of intracellular proteases, caspases, which are responsible for cell death by apoptosis; and (3) inhibiting catabolic/inflammatory responses of chondrocytes by treating them with anti-inflammatory agents such as tumor necrosis factor-α antagonists. Future studies should focus on identifying the appropriate timing for treatment and an appropriate combination of anti-inflammatory, chondro- and matrix-protective biologics to limit the progression of trauma-induced cartilage degeneration and prevent the development of PTOA in the ankle joint., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Joint injuries are common, especially among young adults aged 18 to 44 years. They are accompanied by a cascade of events that increase the risk of posttraumatic osteoarthritis (PTOA). Therefore, understanding of biological responses that predispose to PTOA should help in determining treatment modalities to delay and/or prevent the onset and progression of the disease. The vast majority of the literature pointed to chondrocyte death and apoptosis, inflammation and matrix damage/fragmentation being the earliest events that follow joint trauma. Together these events lead to the development of osteoarthritis-like focal cartilage lesions that if untreated have a tendency to expand and progress to fully developed disease. Currently, the only treatments available for joint trauma are surgical interventions. Experimental biologic approaches involve engineering of cartilage with the use of cells (stem cells or chondrocytes), juvenile or adult cartilage pieces, scaffolds, and various polymeric matrices. The major challenge for all of them is regeneration of normal functional mature hyaline cartilage that can sustain the load, resist compression, and most important, integrate with the host tissue. If the tissue is spontaneously repaired it fails to reproduce original structure and function and thus, may be more susceptible to re-injury. Thus, there is a critical need to develop novel molecular mechanism-based therapeutic approaches to biologic chondral and/or osteochondral repair. The focus of this review is on the earliest molecular and cellular manifestations of injury that can be grouped based on the following therapeutic options for PTOA: chondroprotection, anti-inflammatory, matrix protection, and matrix remodeling/matrix synthesis.