Less flexible and adaptable sensorimotor systems associated with Chronic Ankle Instability (CAI) limit the detection of relevant sensory feedback information, resulting in decreased movement variability. Consequently, when faced with challenging environmental constraints, particularly with conditions that manipulate sensory feedback, individuals with CAI may become more prone to repetitive ankle sprains. This study aimed to investigate the neural control underlying postural control in the injured-limb during increased environmental constraints with sensory feedback manipulations in individuals with and without CAI, respectively.

Forty-two individuals with and without CAI participated in the study and completed the sensory organization test (SOT). The SOT assesses the ability to integrate primary sensory feedback across six conditions that manipulate somatosensory and visual feedback with a combination of a sway-referenced support surface and visual surroundings. The nonlinear method of sample entropy (SampEN) was used to quantify the neural control underlying postural control. A one-way ANOVA examined group differences in neural control during the SOT conditions while standing on the injured-limb.

Individuals with CAI demonstrated significantly lower SampEN while maintaining posture in conditions where they were forced to rely exclusively on vestibular feedback in the injured-limb compared to healthy controls (P < 0.05).

Individuals with CAI did not demonstrate decreased movement variability (neural control) in most of the six SOT conditions. However, the CAI group exhibited decreased movement variability, specifically when they had to rely on vestibular feedback while maintaining posture in the injured-limb compared to healthy controls. Future studies should investigate how manipulation of vestibular feedback affects movement variability with gait in individuals with CAI.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in the early stages of post-traumatic osteoarthritis (PTOA), when symptoms are minimal, and patients remain physically active. To ensure effective therapy, DMOAD delivery systems therefore must withstand repeated mechanical loading without altering the kinetics of drug release. While soft materials are typically preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt controlled drug release. In this study, we present a mechanically resilient soft hydrogel that rapidly self-heals under conditions simulating human running while maintaining sustained release of the cathepsin-K inhibitor L-006235, used as a proof-of-concept DMOAD. This hydrogel demonstrated superior performance compared to a previously reported hydrogel designed for intra-articular drug delivery, which, in our study, neither recovered its structure nor maintained drug release under mechanical loading. When injected into mouse knee joints, the hydrogel provided consistent release kinetics of the encapsulated drug in both treadmill-running and nonrunning mice. In a mouse model of severe PTOA exacerbated by treadmill-running, the L-006235 hydrogel significantly reduced cartilage degeneration, whereas the free drug did not. Overall, our data underscore the hydrogel's potential for treating PTOA in physically active patients.

Traumatic injuries are associated with significant acute pain and subsequent high risk of the development of chronic pain. However, addressing pain after skeletal trauma presents a complex challenge to achieve effective pain relief that minimizes risk of addiction and does not interfere with functional recovery. The Orthopaedic Trauma Association's 2023 Basic Science Focus Forum aimed to bridge the gap between basic science and clinical outcomes with an educational symposium on pain management designed to foster collaboration and provide practical strategies from the frontiers of pain research. Owing to the subjective and multifaceted nature of pain, the development of effective preclinical and clinical pain assessment measures is the first step to making impactful progress in studying pain. Preclinical models prove a valuable tool for studying the molecular mechanisms associated with pain following orthopaedic trauma. These models also allow study of the efficacy of novel pain management techniques, such as testing novel analgesics. Translating novel analgesics and pain management strategies to the clinic requires that we have accurate methods to describe pain to determine whether new approaches are meaningful. It is also necessary to recognize the patient's role and the importance of patient education in the prevention of pain medication misuse, particularly in light of the current national opioid crisis. Overall, collaboration with orthopaedic surgeons in the application of these strategies in a clinical setting is vital for addressing the downfalls of current pain management efforts and providing patients with safe and effective improvements in pain relief after skeletal trauma.

This study aimed to examine the differential expression profiles of plasma metabolites in rat models of post-traumatic osteoarthritis (PTOA) and elucidate the roles of metabolites and their pathways in the progression of PTOA using bioinformatics analysis.

Plasma samples were collected from 24 SD female rats to model PTOA, and metabolomic assays were conducted. The samples were divided into three groups: the surgically induced mild PTOA group (Group A: 3 weeks postoperative using the modified Hulth model; age 2 months), the surgically induced severe PTOA group (Group B: 5 weeks postoperative using the modified Hulth model; age 2 months), and the normal control group (Group C: healthy rats aged 2 months). Metabolites were structurally identified by comparing the retention times, molecular masses, secondary fragmentation spectra, collision energies, and other metabolite data with a database (provided by Shanghai Applied Protein Technology Co., Ltd.). Target prediction and pathway analysis were subsequently performed using bioinformatics analysis.

The experiment revealed that in the mild PTOA group, levels of Alpha-ketoglutarate, Isocitric acid, Dichloroacetate, and other metabolites increased significantly compared with the normal group, whereas Linolenic acid, Lactose, and others decreased significantly. These findings suggest that these metabolites can serve as biomarkers for the diagnosis of early PTOA. In the severe PTOA group, Diosgenin, Indoleacrylic acid, Alpha-ketoglutarate, Isocitric acid, and others were elevated and may also be used as biomarkers for PTOA diagnosis. Adrenosterone, (+)-chlorpheniramine, and Phenanthridine levels were higher in the severe PTOA group compared to the mild PTOA group, while Menadione, Adenosine 5'-monophosphate, and Arg-Gly-Asp levels were lower.

Taurocholate, indoleacrylic acid, alpha-ketoglutarate, and isocitric acid may serve as biomarkers for PTOA joint injury in rats. Menadione, adenosine 5'-monophosphate, and Arg-Gly-Asp exhibited differential expression between severe and mild PTOA groups in rats, potentially reflecting the injury's severity. Further investigation into these molecules in human tissues is warranted to ascertain their utility as biomarkers for PTOA in humans.

This study aims to analyze the impact of different surgical procedures on the prognosis and psychological state of patients with end-stage ankle arthritis (ESAA) by comparing two groups of patients with ESAA who have undergone total ankle replacement (TAR) and ankle arthrodesis (AA), and to investigate whether preoperative psychological status can alter the final clinical outcomes.

This study retrospectively collected data from 66 patients with ESAA who underwent AA surgery in the Foot and Ankle Surgery Department of Xi'an Honghui Hospital between 2016 and 2023. In July 2024, the final follow-up of patients was conducted via telephone or WeChat, with a follow-up duration of no less than 12 months. Before surgery and at the final follow-up, evaluations were conducted using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the Visual Analogue Scale (VAS) for pain (ranging from 0 to 100mm), and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score. The study compared differences in pain scores, functional scores, and psychological scores between patients in the TAR and AA groups before surgery and at the final follow-up. Additionally, patients who underwent TAR and AA were further subgrouped based on the severity of their preoperative psychological status, in order to analyze the impact of preoperative psychological conditions on surgical prognosis.

A total of 66 patients with ESAA completed the follow-up. At the final follow-up, both the VAS and AOFAS scores in the TAR group and the AA group showed significant improvement compared to preoperative levels. Among them, the TAR group performed better in terms of AOFAS scores, but no significant difference was observed in VAS scores between the two groups. Additionally, there was no significant difference in HADS scores between the two groups at the final follow-up. Regardless of whether they belonged to the high-HADS group or the low-HADS group, patients showed significant improvement in clinical scores compared to preoperative levels. However, at the final follow-up, the clinical scores of the high-HADS group were significantly lower than those of the low-HADS group, and the incidence of complications in the high-HADS group was also higher.

This study found that both TAR and AA significantly improved patients' psychology, pain, and functional activities. Both surgical methods demonstrated similar improvements in terms of final psychological status and pain relief. However, patients in the TAR group showed better ankle function and mobility. Patients with poorer preoperative psychological status had worse clinical outcomes and faced a higher risk of complications. The study indicates that both TAR and AA are effective treatment options for patients with ESAA, but poor preoperative psychological status is one of the important risk factors for poor prognosis. Therefore, when selecting a treatment approach, the patient's psychological state and needs should be fully considered, and necessary psychological interventions and postoperative rehabilitation plans should be implemented to enhance the patient's treatment outcomes and quality of life.

Chronic inflammation following knee injuries often results in persistent knee pain and post-traumatic osteoarthritis (PTOA). Understanding the inflammatory processes that follow a joint injury is crucial to effectively mitigate PTOA progression. While inflammation is an integral part of any healing response, unresolved, long-lasting inflammation can be detrimental to the joint. The resolution of inflammation is an active process coordinated by pro-resolving molecules, including specialized pro-resolving mediators (SPMs). While SPMs have been primarily studied in chronic inflammatory diseases, their role in degenerative knee conditions such as PTOA remains underexplored.

This review examines the process of inflammation and its resolution following knee joint injuries and subsequent PTOA, with a focus on the impact of SPMs.

SPMs play a key role in the resolution of inflammation and may offer potential benefits in the management of knee injuries to improve pain and prevent PTOA.

To investigate the role of osteoclast-derived apoptotic bodies (OC-ABs) in osteoarthritis (OA), specifically their impact on subchondral bone remodeling and disease progression, and to explore potential therapeutic strategies targeting OC-AB-induced pathways.

We utilized a mouse model of anterior cruciate ligament transection (ACLT) to simulate post-traumatic osteoarthritis (PTOA). Levels of OC-ABs were assessed in subchondral bone and correlated with OA severity. Additionally, apoptotic body-deficient MRL/lpr mice were analyzed to evaluate the direct contribution of OC-ABs to OA progression and subchondral bone remodeling. The involvement of OC-ABs in osteogenesis was further examined using mesenchymal stem cells (MSCs), with a focus on the RANKL reverse signaling pathway. The therapeutic potential of rapamycin to counteract OC-AB effects was tested.

Increased OC-AB accumulation in subchondral bone was positively correlated with OA severity in ACLT-induced mice. Apoptotic body-deficient MRL/lpr mice demonstrated slower OA progression and maintained more stable subchondral bone architecture, indicating a pathogenic role of OC-ABs in OA. OC-ABs significantly stimulated osteogenesis in MSCs via the RANKL reverse signaling pathway. Treatment with rapamycin effectively reversed OC-AB-induced subchondral bone formation, mitigated OA progression, and inhibited the RANKL reverse signaling pathway.

OC-ABs play a critical role in exacerbating OA by promoting subchondral bone remodeling via the RANKL reverse signaling pathway. Rapamycin presents as a promising therapeutic agent capable of mitigating OC-AB-driven pathology, highlighting new avenues for targeted OA treatment.

Despite quadriceps weakness in individuals after quadriceps tendon anterior cruciate ligament reconstruction (QT-ACLR), and its association with knee joint mechanics, no studies have addressed gait mechanics in both partial-thickness (PT-Q) and full-thickness (FT-Q) options for QT-ACLR.

To assess gait mechanics across a QT-ACLR cohort. We hypothesized that QT-ACLR would show changes in knee joint mechanics compared to control participants (CON) and nonoperated limbs. Additionally, we hypothesized that FT-Q operated limbs would show greater changes compared to PT-Q and CON.

Retrospective cohort study.

University-affiliated sports medicine institute.

Sixteen patients who underwent QT-ACLR (7 FT-Q: Age (years) = 28.6 ± 7.3, post-op (months) = 23.5 ± 10.7, 9 PT-Q: Age = 25.2 ± 4.3, post-op = 24.4 ± 11.7) were recruited and compared to 11 CON (age = 23.4 ± 4.8).

Participants underwent gait testing with force plate integrated motion capture.

Mixed repeated-measures analyses of covariance, adjusted for gait speed, were used to determine significant main effects or interactions in peak knee flexion angle, sagittal knee range of motion, peak internal knee extension moment (KEM), and peak internal knee flexion moment.

When measured an average of 2 years after surgery, no main effect for limb or limb by depth interaction were detected. A significant effect by group was observed for peak KEM (p = .03, η2 = .27) and peak knee flexion angle (p = .04, η2 = .24) in the loading response phase. FT-Q (p = .02) and PT-Q (p = .03) showed lower KEM compared to the CON group in both limbs. The FT-Q group showed lower peak knee flexion angle compared to the CON group (p = .01).

Knee joint symmetry may be recovered 2 years following QT-ACLR, but lower KEM compared to CON for both graft options and lower peak knee flexion angle than CON for the FT-Q group may indicate a need for further investigation in QT-ACLR.

Understanding the factors contributing to willingness to participate in randomized clinical trials (RCTs) after anterior cruciate ligament reconstruction (ACLR) is crucial to optimizing recruitment and understanding whether interested participants represent the patient population that may benefit from the studied treatment.

To understand patients' willingness to participate in a future RCT of an oral medication to prevent posttraumatic osteoarthritis (PTOA) after ACLR.

Cross-sectional study; Level of evidence, 3.

A total of 103 patients aged 18 to 45 years who were either planning to undergo ACLR in the next 4 months or had undergone ACLR within 1 year of the screening date were recruited from 2 institutions. The patients viewed a video explaining the trial and completed a questionnaire that included demographic characteristics, pain intensity, activity level, willingness to participate in the hypothetical trial, and their perceived risk (on a scale of 0%-100%) of developing knee PTOA (next 10 years or lifetime).

Within the cohort, 31% stated they were "definitely willing," 38% were "probably willing," 17% were "unsure," and 14% were "unwilling" to participate in a hypothetical trial. Willingness did not differ by pain or activity level; however, younger patients stated they were less willing to participate. The most common reasons for unwillingness to participate included not wanting to take a medication daily (59%) and concerns about medication risks or side effects (59%). Respondents who indicated a definite willingness to participate in the trial had higher perceptions of their own PTOA risk over the next 10 years than those who indicated they would not participate (70% vs 50%).

In this prospective preference assessment, 69% of survey respondents expressed a willingness to participate in an RCT involving an oral medication to potentially alter the progression of PTOA after ACLR. The results suggest that an RCT in this study should include clear and concise information on the risk of developing PTOA after ACLR and the safety and tolerability of study medications in the recruitment materials.

Knee post-traumatic osteoarthritis (PTOA) often develops in younger populations following anterior cruciate ligament (ACL) rupture, accounting for 12% of all symptomatic osteoarthritis (OA). The current literature implicates gait asymmetry in late-stage knee OA progression; however, early-knee PTOA development involvement is ill defined. This study explored gait asymmetry involvement in early-stage knee PTOA following ACL ruptures. Gait asymmetry, measured as asymmetry in duty factor (relative contact time), and joint loading data were collected, using infrared-camera motion capture and Kistler force plates for participants exhibiting either historical ACL ruptures (ACL+; n = 4) or no previous joint trauma (ACL-; n = 11). Joint loading measures included external knee adduction moment (EKAM) and external knee flexion moment (KFM), early (peak 1; EKAMp1 and KFMp1) and late (peak 2; EKAMp2 and KFMp2), stance peaks (Nm/kg), and respective time integrals (Nm·ms/kg; iEKAMp1, iEKAMp2, iKFMp1, and iKFMp2). ACL+ exhibited greater asymmetrical duty factor (78% difference) and greater joint load differences: EKAMp1 (26%), EKAMp2 (49%), KFMp1 (37%), iKFMp1 (44%), and iKFMp2 (60%). Significant relationships were found between duty factor asymmetry and both KFMp2 (R2 = 0.665) and iKFMp2 (R2 = 0.504). These preliminary data suggest gait asymmetry-induced joint loading may contribute to knee PTOA progression, but further research with increased sample sizes and the quantitative assessment of cartilage status is required.

Improvements in the treatment of cartilage require insights into the secretory profile of mesenchymal stem cells (MSCs). Apart from their differentiation potential, MSCs secrete a multitude of molecules with therapeutic properties that benefit chondrogenesis and immunomodulation. Previously, we employed a small-panel microarray to demonstrate differences within conditioned medium (CM) of MSCs that were mechanically stimulated within a joint-mimicking bioreactor and their unloaded controls. This study analyzed the proteomic content within CM from 4 week mechanically loaded MSCs with a larger protein microarray. We examined the chondrogenic effect of CM by administration to MSC and chondrocyte pellet cultures, as well as functional changes in T cell proliferation. CM from mechanically loaded samples shows a promising push towards chondrogenic phenotypes within both pellet cultures. Inhibition of T cell proliferation was also observed. This in vitro model could enhance our understanding how mechanical load induces changes in MSC secretome benefitting cartilage healing.

Joint injury is a risk factor for post-traumatic osteoarthritis. However, metabolic and microarchitectural changes within the joint post-injury in both sexes remain unexplored. This study identified tissue-specific and spatially-dependent metabolic signatures in male and female mice using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and LC-MS metabolomics. Male and female C57Bl/6J mice were subjected to non-invasive joint injury. Eight days post-injury, serum, synovial fluid, and whole joints were collected for metabolomics. Analyses compared between injured, contralateral, and naïve mice, revealing local and systemic responses. Data indicate sex influences metabolic profiles across all tissues, particularly amino acid, purine, and pyrimidine metabolism. MALDI-MSI generated 2D ion images of bone, the joint interface, and bone marrow, highlighting increased lipid species in injured limbs, suggesting physiological changes across injured joints at metabolic and spatial levels. Together, these findings reveal significant metabolic changes after injury, with notable sex differences.

Persistent pain is a complicated phenomenon associated with a wide array of complex pathologies and conditions (e.g., complex regional pain syndrome, non-freezing cold injury), leading to extensive disability and reduced physical function. Conventional resistance training is commonly contraindicated in load compromised and/or persistent pain populations, compromising rehabilitation progression and potentially leading to extensive pharmacological intervention, invasive procedures, and reduced occupational status. The management of persistent pain and utility of adjunct therapies has become a clinical and research priority within numerous healthcare settings, including defence medical services.

Blood flow restriction (BFR) exercise has demonstrated beneficial morphological and physiological adaptions in load-compromised populations, as well as being able to elicit acute hypoalgesia. The aims of this narrative review are to: (1) explore the use of BFR exercise to elicit hypoalgesia; (2) briefly review the mechanisms of BFR-induced hypoalgesia; (3) discuss potential implications and applications of BFR during the rehabilitation of complex conditions where persistent pain is the primary limiting factor to progress, within defence rehabilitation healthcare settings. The review found BFR application is a feasible intervention across numerous load-compromised clinical populations (e.g., post-surgical, post-traumatic osteoarthritis), and there is mechanistic rationale for use in persistent pain pathologies. Utilisation may also be pleiotropic in nature by ameliorating pathological changes while also modulating pain response. Numerous application methods (e.g., with aerobic exercise, passive application, or resistance training) allow practitioners to cater for specific limitations (e.g., passive, or contralateral application with kinesiophobia) in clinical populations. Additionally, the low-mechanical load nature of BFR exercise may allow for high-frequency use within residential military rehabilitation, providing a platform for conventional resistance training thereafter.

Future research needs to examine the differences in pain modulation between persistent pain and pain-free populations with BFR application, supporting the investigation of mechanisms for BFR-induced hypoalgesia, the dose-response relationship between BFR-exercise and pain modulation, and the efficacy and effectiveness of BFR application in complex musculoskeletal and persistent pain populations.

Non-weightbearing or immobilization after anterior cruciate ligament (ACL) reconstruction accelerates cartilage degeneration. However, it is unclear whether these adverse effects are reversed by reloading or remobilization. Moreover, it is unknown whether the combination of non-weightbearing and immobilization after ACL reconstruction has synergistic effects on cartilage degeneration. We aimed to determine 1) the long-term effects of reloading or remobilization following short-term non-weightbearing or immobilization after ACL reconstruction on cartilage degeneration and 2) the combined effects of non-weightbearing and immobilization on cartilage degeneration. We divided ACL-reconstructed rats into four groups: no intervention, non-weightbearing, joint immobilization, and non-weightbearing plus immobilization. Non-weightbearing and immobilization were performed for 2 weeks, after which all rats were reared without intervention. Untreated rats were used as controls. At 2, 4, or 12 weeks after starting the experiment, cartilage degeneration in the anterior, middle, and posterior regions of the medial tibial plateau was histologically assessed. Two weeks of non-weightbearing or immobilization after ACL reconstruction facilitated cartilage degeneration in the middle and posterior regions compared to those with no intervention. Cartilage degeneration was not reversed by 10 weeks of reloading or remobilization. Compared with non-weightbearing alone, combination of non-weightbearing and immobilization improved cartilage degeneration in the middle region, but worsened it in the posterior region. Cartilage degeneration induced by 2 weeks of non-weightbearing or immobilization after ACL reconstruction was not reversed by reloading or remobilization. Thus, to reduce cartilage degeneration, non-weightbearing and immobilization should be avoided after ACL reconstruction, even for short-term.

Treatment of ankle osteoarthritis by total ankle replacement (TAR) is increasing worldwide. The aim of the study was to present the overall temporal trends of TAR throughout 22 years (2001-2022) in Italy, analyzing the distributions of hospitals by volume of activity and patients by age and sex, drawing on the National Hospital Discharge Record database. Furthermore, as a secondary aim, we compared these trends with those of ankle fusions.

International Classification of Diseases, 9th Revision, Clinical Modification (ICD9-CM) codes of interest were identified to browse the Italian National Hospital Discharge Record database. Surgical volumes, trends over time, classes of hospital activity volume, sex and age of patients, and population incidence rates were described. The statistical significance of time series trends was assessed by the Cox-Stuart test with randomness as a null hypothesis.

20,248 ankle procedures (total ankle replacements 8853 and ankle fusions 11,395) were extracted from 231,601,523 admissions registered nationally from 2001 to 2022. The yearly total number of TARs significantly increased almost tenfold from 96 to 996 (p < 0.05), while the number of fusions exhibited a stationary behavior (p > 0.05). The increased trend in TAR procedures was concentrated mostly in the North of Italy, with predominantly males between 55 and 64 years of age. The analysis of the number of procedures performed on inhabitants by region and that performed by all the hospitals in the region showed a different pattern across Italy.

The substantial increase in TARs may be owing to improved implant designs and innovative surgical technologies, which allow the treatment of more severe cases and deformities, previously untreated or treated by a fusion. This trend highlights the need to invest in implementing high quality registries by promoting surgeons' participation in data collection.

population based study, level 1 evidence.

The complement system is locally activated after joint injuries and leads to the deposition of the terminal complement complex (TCC). Sublytic TCC deposition is associated with phenotypical alterations of human articular chondrocytes (hAC) and enhanced release of inflammatory cytokines. Chronic inflammation is a known driver of chondrosenescence in osteoarthritis (OA). Therefore, we investigated whether TCC deposition contributes to stress-induced premature senescence (SIPS) during aging in vivo and after ex vivo cartilage injury.

Femoral condyles of male 13-week-old and 72-week-old CD59-ko (higher TCC deposition), C6-deficient (insufficient TCC formation), and C57BL/6 (WT) mice were collected to assess age-related OA. Furthermore, macroscopically intact human and porcine cartilage explants were traumatized and cultured with/without 30% human serum (HS) to activate the complement system. Explants were additionally treated with clusterin (CLU, TCC inhibitor), N-acetylcysteine (NAC, antioxidant), Sarilumab (IL-6 receptor inhibitor), STAT3-IN-1 (STAT3 inhibitor), or IL-1 receptor antagonist (IL-1RA) in order to investigate the consequences of TCC deposition. Gene and protein expression of senescence-associated markers such as CDKN1A and CDKN2A was determined.

In the murine aging model, CD59-ko mice developed after 72 weeks more severe OA compared to C6-deficient and WT mice. mRNA analysis revealed that the expression of Cdkn1a, Cdkn2a, Tp53, Il1b, and Il6 was significantly increased in the cartilage of CD59-ko mice. In human cartilage, trauma and subsequent stimulation with HS increased mRNA levels of CDKN1A, CDKN2A, and IL6, while inhibition of TCC formation by CLU reduced the expression. Antioxidative therapy with NAC had no anti-senescent effect. In porcine tissue, HS exposure and trauma had additive effects on the number of CDKN2A-positive cells, while Sarilumab, STAT-IN-1, and IL-1RA reduced CDKN2A expression by trend.

Our results demonstrate that complement activation and consequent TCC deposition is associated with chondrosenescence in age-related and trauma-induced OA. We provided evidence that the SIPS-like phenotype is more likely induced by TCC-mediated cytokine release rather than oxidative stress. Overall, targeting TCC formation could be a future approach to attenuate OA progression.

Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve. To better understand molecular programs contributing to PTOA development or resolution, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell RNA sequencing of synovial joints in PTOA-susceptible C57BL/6J (B6) and PTOA-resistant MRL/MpJ (MRL) mice. We identified significant differences in monocyte and macrophage subpopulations between MRL and B6 joints. A potent myeloid-driven anti-inflammatory response was observed in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. Multiple CD206+ macrophage populations classically described as M2 were found enriched in MRL injured joints. These CD206+ macrophages also robustly expressed Trem2, a receptor involved in inflammation and myeloid cell activation. These data suggest that the PTOA resistant MRL mouse strain displays an enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated M2 macrophages within the synovial tissue and joint space.

To evaluate whether cumulative impact load and serum biomarkers are related to lower-extremity injury and to determine any impact load and cartilage biomarker relationships in collegiate female basketball athletes.

This was a prospective longitudinal study evaluating lower-extremity impact load, serum cartilage biomarkers, and injury incidence over the course of a single collegiate women's basketball season. Data were collected from August 2022 to April 2023; no other follow-up after the cessation of the season was conducted in this cohort. Inclusion criteria for the study included collegiate women's basketball athletes, ages 18 to 25 years, who were noninjured at the start of the study time frame (August 2024). Cartilage synthesis (procollagen II carboxy propeptide and aggrecan chondroitin sulfate 846 epitope) and degradation (collagen type II cleavage) biomarkers were evaluated at 6 season timepoints. Impact load metrics (cumulative bone stimulus, impact intensity) were collected during practices using inertial measurement units secured to the distal medial tibiae. Injury was defined as restriction of participation for 1 or more days beyond day of initial injury. Cumulative impact load metrics were calculated over the week before any documented injury and blood draws for analysis. Point biserial and Pearson product moment correlations were used to determine the relationship between impact load metrics, serum biomarkers, and injury.

Eleven collegiate women's basketball athletes (height: 1.86 meters, mass: 82.0 kg, age: 20.54 years) participated. Greater medium-range (6-20 g) cumulative impact intensities during week 5 and 6 for both limbs (r = 0.674, P = .023) and high-range (20-200 g) during week 8 for both limbs (0.672, P = .024) were associated with injury. Greater cumulative bone stimulus was associated with increased procollagen II carboxy propeptide levels before conference playoffs for right (r = 0.694, P = .026) and left (r = 0.747, P = .013) limbs. Greater chondroitin sulfate 846 epitope levels at off-season-1 (r = 0.729, P = .017), and at the beginning of the competitive season (r = 0.645, P = .044) were associated with season-long injury incidence.

In this study, we found that moderate-to-high intensity impacts (6-200 g) early in the season were associated with subsequent injury among female collegiate basketball players. Increased cartilage synthesis at various time points was correlated with increased cumulative bone stimulus metrics and season-long injury incidence in this population.

Level IV, prognostic case series.

Osteoarthritis (OA), a degenerative disease marked by cartilage erosion and synovial proliferation, has led to an increased interest in natural plant-based compounds to slow its progression. Pristimerin(Pri), a triterpenoid compound derived from Tripterygium wilfordii, has demonstrated anti-inflammatory and antioxidant characteristics. This study explores the protective effects of Pri on OA and its potential mechanisms.

In this study, we examined the impact of Pri on the expression of inflammatory factors and extracellular matrix(ECM) degradation induced by IL-1β in chondrocyte experiments. Bioinformatics analysis was then performed to investigate the potential signaling pathways involved in Pri's protective effects. Finally, the efficacy of Pri in reducing cartilage degradation was further evaluated in a destabilization of the medial meniscus (DMM) mouse model.

Utilizing bioinformatics analysis and in vitro studies, it was revealed that Pri inhibits the activation of NF-κB and MAPK signaling pathways, leading to the reversal of upregulated MMP-13 (matrix metalloproteinases-13), iNOS (inducible nitric oxide synthase), and COX-2(cyclooxygenase-2) elicited by IL-1β stimulation, as well as the partial restoration of Collagen-II levels. Furthermore, in a DMM mouse model, the group treated with Pri exhibited reduced cartilage degradation and slowed OA progression compared to the modeling group.

This research highlights Pri as a potential therapeutic agent for delaying OA progression.

The onset of degenerative joint diseases such as post-traumatic osteoarthritis (PTOA) are associated with joint injury, biomechanical changes, and synovial biochemical anomalies. Sex and reproductive endocrinology have been emerging as potential risk factors, with epidemiological evidence revealing that female's exhibit higher PTOA risk and poorer outcomes post-injury compared to males. Sex hormones, including estradiol, progesterone, and testosterone, have been shown to regulate inflammatory signaling in immune and synovial cells, yet their collective impact on injury-induced joint inflammation and catabolism is poorly understood. Using an in silico kinetic model, we investigated the effects of sex-specific endocrine states on post-injury mechanisms in the human synovial joint. Our model results reveal that heightened estradiol levels in pre-menopausal females during the peri-ovulatory phase increase interleukin (IL)-1β expression and suppress IL-10 expression within the synovium after a simulated injury. Conversely, elevated testosterone levels in males decrease post-injury IL-1β, tumor necrosis factor alpha (TNF)-α, and stromelysin (MMP)-3 expression while increasing IL-10 production compared to females. Gaining insight into the effects of sex hormones on injury-induced inflammation and cartilage degradation provides a basis for designing future experimental and clinical studies to explore their effects on the synovial system, with a particular focus on the female sex.

Osteoarthritis (OA) is a common degenerative joint condition caused by an imbalance between cartilage synthesis and degradation, which disrupts joint homeostasis. This study investigated the anti-inflammatory and joint-improving effects of Pinus densiflora root extract powder (PDREP) in both in vitro and in vivo OA models.

In an in vitro OA model, in which SW1353 human chondrosarcoma cells were treated with interleukin (IL)-1β, PDREP treatment significantly reduced the mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 while enhancing collagen type II alpha 1 (Col2a1) mRNA level, and decreased IL-6 and prostaglandin E2 (PGE2) levels. In addition, PDREP inhibited the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), p38, nuclear factor-kappa B (NF-κB), and the expression of inducible nitric oxide synthase (iNOS). In a monosodium iodoacetate (MIA)-induced OA rat model, the administration of PDREP resulted in decreased OA clinical indices, improved weight-bearing indices and gait patterns, reduced histological damage, and lowered serum inflammatory cytokine and MMPs expression. Furthermore, PDREP downregulated the phosphorylation of ERK, JNK, p38, and NF-κB, as well as the expression of iNOS, consistent with the in vitro findings.

These results suggest that PDREP exhibits anti-inflammatory and joint-improving effects and has potential as a therapeutic strategy or functional food for the treatment of OA.

The purpose of this study was to compare the incidence of knee osteoarthritis (OA) between the anatomic single-bundle (SB) and anatomic double-bundle (DB) anterior cruciate ligament (ACL) reconstruction technique after 5-year follow-up (FU). Secondary objectives were to compare patient-reported outcome measures (PROMs), clinical examination, activity level, functional tests and graft failures between the two groups.

The study was a secondary analysis after 5-year FU of a randomized controlled trial (RCT) (Clinical Trials NCT01033188). One hundred and twenty patients between 18 and 40 years were randomized to either anatomic SB or anatomic DB reconstruction. The Kellgren-Lawrence (KL) classification grade ≥2 and the Osteoarthritis Research Society International (OARSI) atlas criteria score ≥2 were used for defining OA. Additionally, PROMs were obtained and clinical examinations of the knees were performed. Finally, the number of patients experiencing graft failure in each group was recorded.

Radiographic imaging was performed in 39 patients in the SB group and in 37 patients in the DB group. Four patients (10%) in the SB group and two (5%) in the DB group developed osteoarthritis according to the KL classification (p = 0.28). Five (13%) in the SB group and three (8%) in the DB group developed osteoarthritis according to the OARSI atlas criteria (p = 0.59; difference 5.0% [95% confidence interval, CI: -0.10 to 0.20]). There were no significant differences in the PROMs, clinical examinations, activity levels, or functional tests when comparing the two groups. Of initially 62 SB patients, 14 (23%) experienced graft failure compared to 4 (7%) of the 58 DB patients (p = 0.015; difference 0.016 [95% CI: 0.03-0.29]).

At 5-year FU, there were no significant differences in the incidence of OA, PROMS, or other clinical findings comparing the anatomic DB to anatomic SB ACL reconstructed patients. There were fewer graft failures among patients treated with anatomic DB ACL reconstruction.

II.

The success of unicompartmental knee arthroplasty (UKA) for monocompartmental knee arthritis is reliant on appropriate patient selection. This article addresses the clinical challenges that may arise when attempting to identify patients likely to have favorable outcomes following UKA. Despite advancements of implant design and accuracy of surgical tools, considerable challenges persist in predicting patient specific success and satisfaction following UKA. Variation in patient characteristics, healthcare practices, and outcomes in the literature make the establishment of a strict set of universal guidelines difficult. This article will provide a comprehensive overview of the current landscape of patient selection for UKA, acknowledging the existing clinical dilemmas and challenges faced by clinicians and proposing avenues for future research including the integration of patient predictive models, advanced imaging, and artificial intelligence to enhance predictive accuracy.

Brominated domain protein 4 (BRD4) is a chromatin reader known to exacerbate the inflammatory response in post-traumatic osteoarthritis (PTOA) by controlling the expression of inflammatory cytokines. However, the extent to which this regulatory effect is altered after BRD4 translation remains largely unknown. In this study, we showed that the E3 SUMO protein ligase CBX4 (Cbx4) is involved in the SUMO modification of BRD4 to affect its ability to control the expression of the proinflammatory genes IL-1β, TNF-α, and IL-6 in synovial fibroblasts. Specifically, Cbx4-mediated SUMOylation of K1111 lysine residues prevents the degradation of BRD4, thereby activating the transcriptional activities of the IL-1β, TNF-α and IL-6 genes, which depend on BRD4. SUMOylated BRD4 also recruits the multifunctional methyltransferase subunit TRM112-like protein (TRMT112) to further promote the processing of proinflammatory gene transcripts to eventually increase their expression. In vivo, treatment of PTOA with a Cbx4 inhibitor in rats was comparable to treatment with BRD4 inhibitors, indicating the importance of SUMOylation in controlling BRD4 to alleviate PTOA. Overall, this study is the first to identify Cbx4 as the enzyme responsible for the SUMO modification of BRD4 and highlights the central role of the Cbx4-BRD4 axis in exacerbating PTOA from the perspective of inflammation.

There have not been any clear studies on the use of mesenchymal stem cells (MSCs) to treat osteoarthritis (OA) in the knee.

This study investigates the effects of different MSC dosages on pain alleviation in individuals with OA in the knee by conducting a meta-analysis of existing randomized controlled trials. Electronic resources such as Google Scholar, PubMed, Cochrane Library, and Web of Science were searched up until June 2023. Treatment effect sizes were computed using the knee osteoarthritis outcome score (KOOS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Knee Society Score (KSS). Random or fixed effect models were applied to aggregate the data. We performed a subgroup analysis according to dosage level. The heterogeneity of the research was investigated using the Chi-square test and the I2 index.

The meta-analysis included 26 studies with a total sample size of 739 patients. A significant reduction in pain was observed 1 year and 2 years following the injection of MSCs into the injured joint, as indicated by the Visual Analogue Scale, WOMAC, KOOS, and KSS indexes (P < 0.05). Patients on MSCs reported much reduced pain after 1 and 2 years compared to the control group (P < 0.05). Subgroup and meta-regression analyses revealed no statistically significant variations in the effectiveness of MSC dosage (P < 0.05). The studies did not report any adverse effects.

Different dosages of MSCs had the same pain-relieving effects on patients with OA in the knee. MSC injections were safe and beneficial in such cases.

Galectin-9 (LGALS9) plays an important role in the occurrence and development of many diseases, including immunity, infection, cancer, etc. Studies have found that LGALS9 can phosphorylate ERK1/2 in the MAPK pathway. However, there is currently no clear conclusion on the role of LGALS9 in OA, and it is worth further exploring the regulatory role and mechanism of LGALS9 in OA in this study. In the initial stage, we collected 6 cases of hip joint soft tissue from normal individuals and 6 cases from OA patients clinically to analyze the differential expression of LGALS9 between normal individuals and OA patients; Subsequently, RNAi technology was used to preliminarily clarify the regulatory role of LGALS9 in an in vitro OA model; Then, lentivirus was used to knock down and overexpress LGALS9, and in vivo and in vitro OA models were constructed. QRT-PCR, western blot, safranin fast green staining (SO), immunofluorescence and other experimental methods were used to quantitatively analyze inflammatory and signaling pathway indicators, further improving the regulatory effect of LGALS9 on inflammation and the pathogenesis of OA.

Osteoarthritis is a heterogeneous disease. The objective was to compare differences in underlying cellular mechanisms and endogenous repair pathways between synovial fluid (SF) from male and female participants with different injuries to improve the current understanding of the pathophysiology of downstream post-traumatic osteoarthritis (PTOA).

SF from n = 33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. SF was extracted and analyzed via liquid chromatography-mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies (ligament, meniscal, and combined ligament and meniscal) and patient sex. Samples were pooled and underwent secondary fragmentation to identify metabolites.

Different knee injuries uniquely altered SF metabolites and downstream pathways including amino acid, lipid, and inflammatory-associated metabolic pathways. Notably, sexual dimorphic metabolic phenotypes were examined between males and females and within injury pathology. Cervonyl carnitine and other identified metabolites differed in concentrations between sexes.

These results suggest that different injuries and patient sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries, sex, and PTOA development may yield data regarding how endogenous repair pathways differ between male and female injury types. Ongoing metabolomic analysis of SF in injured male and female patients can be performed to monitor PTOA development and progression.

Articular cartilage damage and degeneration are among hallmark manifestations of joint injuries and arthritis, classically osteoarthritis. Cartilage compositional MRI (Cart-C MRI), a quantitative technique, which aims to detect early-stage cartilage matrix changes that precede macroscopic alterations, began development in the 1990s. However, despite the significant advancements over the past three decades, Cart-C MRI remains predominantly a research tool, hindered by various technical and clinical hurdles. This paper will review the technical evolution of Cart-C MRI, delve into its clinical applications, and conclude by identifying the existing gaps and challenges that need to be addressed to enable even broader clinical application of Cart-C MRI.

Patellofemoral arthroplasty (PFA) is emerging as an attractive alternative to total knee arthroplasty (TKA) for isolated patellofemoral-osteoarthritis (PF-OA) for selected patients. The success of PFA is highly dependent on patient selection. This intervention is still burdened with a higher rate of revisions and a lower survival rate than TKA when the indications or the surgical technique are not optimal. We highlight the indications and contraindications of PFA to obtain satisfying functional outcomes and survivorship. Preoperative clinical and radiological assessment is critical to determine the presence of PFA indications, the absence of contraindications and the necessity of any associated procedures, particularly for the tibial tubercle. The typical indications are patients with isolated symptomatic PF-OA, with trochlear dysplasia, when bone-on-bone Iwano 4 osteoarthritis is observed, without significant malalignment and with the absence of risk factors for developing progressive tibiofemoral-OA. The three main causes of isolated PF-OA are primary OA, trochlear dysplasia and posttraumatic OA following patellar fracture. Trochlear dysplasia is the preferred indication for PFA. Lack of experience with arthroplasty or realignment of the extensor mechanism is a relative contraindication to performing PFA.

To explore the mechanism and efficacy of gel in the treatment of posttraumatic osteoarthritis (PTOA), combined with hyaluronic acid (HA) and bone marrow mesenchymal stem cell exosomes (BMSC-EXOs), and to explain its role in alleviating oxidative stress damage induced by mitochondrial reactive oxygen species (ROS).

How is the therapeutic potential of toa influenced by bone marrow mesenchymal stem cells-EXO to be evaluated both in vitro and in vivo. In vitro, BMSC-EXOs were extracted and characterized from rat specimens and labeled with Dil. Rat primary chondrocytes were then isolated to create a cellular PTOA model. BMSC-EXOs + HA group, BMSC-EXOs + HA + 740Y-P group, model group, BMSC-EXOs group, HA group, and control group were included in the cell group, and the function of cartilage matrix and the level of oxidative stress could be evaluated. Cartilage matrix integrity and oxidative stress can be assessed by grouping rats. At the same time, a rat model of ptosis can be established by excision of the anterior cruciate ligament, and joint rehabilitation, with pro-inflammatory and Enzyme-linked immunosorbent assay (ELISA) can be used to determine anti-inflammatory markers.

sThe combined use of BMSC-EXOs and HA gel was found to significantly reduce oxidative stress in chondrocytes and PTOA rat models, improving cartilage mechanical properties more effectively than BMSC-EXOs alone.

BMSC-EXOs combined with HA gel offer a promising treatment for PTOA by modulating damage caused by mitochondrial ROS-induced oxidative stress.

Osteoarthritis (OA) is a common chronic disease largely driven by mechanical factors, causing significant health and economic burdens worldwide. Early detection is challenging, making animal models a key tool for studying its onset and mechanically-relevant pathogenesis. This review evaluate current use of preclinical in vivo models and progressive measurement techniques for analysing biomechanical factors in the specific context of the clinical OA phenotypes. It categorizes preclinical in vivo models into naturally occurring, genetically modified, chemically-induced, surgically-induced, and non-invasive types, linking each to clinical phenotypes like chronic pain, inflammation, and mechanical overload. Specifically, we discriminate between mechanical and biological factors, give a new explanation of the mechanical overload OA phenotype and propose that it should be further subcategorized into two subtypes, post-traumatic and chronic overloading OA. This review then summarises the representative models and tools in biomechanical studies of OA. We highlight and identify how to develop a mechanical model without inflammatory sequelae and how to induce OA without significant experimental trauma and so enable the detection of changes indicative of early-stage OA in the absence of such sequelae. We propose that the most popular post-traumatic OA biomechanical models are not representative of all types of mechanical overloading OA and, in particular, identify a deficiency of current rodent models to represent the chronic overloading OA phenotype without requiring intraarticular surgery. We therefore pinpoint well standardized and reproducible chronic overloading models that are being developed to enable the study of early OA changes in non-trauma related, slowly-progressive OA. In particular, non-invasive models (repetitive small compression loading model and exercise model) and an extra-articular surgical model (osteotomy) are attractive ways to present the chronic natural course of primary OA. Use of these models and quantitative mechanical behaviour tools such as gait analysis and non-invasive imaging techniques show great promise in understanding the mechanical aspects of the onset and progression of OA in the context of chronic knee joint overloading. Further development of these models and the advanced characterisation tools will enable better replication of the human chronic overloading OA phenotype and thus facilitate mechanically-driven clinical questions to be answered.

Anterior Cruciate Ligament (ACL) injury initiates post-traumatic osteoarthritis (PTOA) via two distinct processes: initial direct contact injury of the cartilage surface during ACL injury, and secondary joint instability due to the ACL deficiency. Using the well-established Compression-induced ACL rupture method (ACL-R) and a novel Non-Compression ACL-R model, we aimed to reveal the individual effects of cartilage compression and joint instability on PTOA progression after ACL injury in mice.

Twelve-week-old C57BL/6J male were randomly divided to three experimental groups: Compression ACL-R, Non-Compression ACL-R, and Intact. Following ACL injury, we performed joint laxity testing and microscopic analysis of the articular cartilage surface at 0 days, in vivo optical imaging of matrix-metalloproteinase (MMP) activity at 3 and 7 days, and histological and microCT analysis at 0, 7, 14, and 28 days.

The Compression ACL-R group exhibited a significant increase of cartilage roughness immediately after injury compared with the Non-Compression group. At 7 days, the Compression group exhibited increased MMP-induced fluorescence intensity and MMP-13 positive cell ratio of chondrocytes. Moreover, histological cartilage degeneration was observable in the Compression group at the same time point. Sclerosis of tibial subchondral bone in the Compression group was more significantly developed than in the Non-Compression group at 28 days.

Both Compression and Non-Compression ACL injury initiated PTOA progression due to joint instability. However, joint contact during ACL rupture also caused initial micro-damage on the cartilage surface and initiated early MMP activity, which could accelerate PTOA progression compared to ACL injury without concurrent joint contact.

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, affecting hundreds of millions of people globally. Current clinical approaches are confined to providing only symptomatic relief. Research over the past two decades has established that OA is not merely a process of wear and tear of the articular cartilage but involves abnormal remodelling of all joint tissues. Although many new mechanisms of disease have been identified in the past several decades, the efficient and sustainable delivery of drugs targeting these mechanisms in joint tissues remains a major challenge. Nanoparticles recently emerged as favoured delivery vehicles in OA treatment, offering extended drug retention, enhanced drug targeting, and improved drug stability and solubility. In this review, we consider OA as a disease affecting the entire joint and initially explore the pathophysiology of OA across multiple joint tissues, including the articular cartilage, synovium, fat pad, bone, and meniscus. We then classify nanoparticles based on their composition and structure, such as lipids, polymers, inorganic materials, peptides/proteins, and extracellular vesicles. We summarise the recent advances in their use for treatment and diagnosis of OA. Finally, we discuss the current challenges and future directions in this field. In conclusion, nanoparticle-based nanosystems are promising carriers that advance OA treatment and diagnosis.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

Health disparities in osteoarthritis (OA) outcomes exist both in the occurrence and treatment of functional limitation and disability for Mexican Americans. Although the effect of self-management of chronic illness is well established, studies demonstrate little attention to self-management of function or disability, despite the strong potential effect on both and, consequently, on patients' lives.

The purpose of this study pilot was to develop and test key variable relationships for a measure of disability self-management among Mexican Americans.

In this sequential, two-phased, mixed-methods, biobehavioral pilot study of Mexican American women and men with OA, a culturally tailored measure of disability self-management was created, and initial relationships among key variables were explored.

First, a qualitative study of 19 adults of Mexican American descent born in Texas (United States) or Mexico was conducted. The Mexican American Disability Self-Management Scale was created using a descriptive content analysis of interview data. The scale was tested and refined, resulting in 18 items and a descriptive frequency of therapeutic management efforts. Second, correlations between study variables were estimated: Disability and function were negatively correlated. Disability correlated positively with social support and activity effort. Disability correlated negatively with disability self-management, pain, and C-reactive protein. Function was positively correlated with age, pain, and depression. Liver enzymes (alanine transaminase) correlated positively with pain and anxiety.

This mixed-methods study indicates directions for further testing and interventions for disability outcomes among Mexican Americans.

Up to 50% of individuals develop post-traumatic osteoarthritis (PTOA) within 10 years following knee-joint injuries such as anterior cruciate ligament rupture or acute meniscal tear. Lower-extremity PTOA prevalence is estimated to account for ≥12% of all symptomatic osteoarthritis (OA), or approximately 5.6 million cases in the USA. With knowledge of the inciting event, it might be possible to 'catch PTOA in the act' with sensitive imaging and soluble biomarkers and thereby prevent OA sequelae by early intervention. Existing biomarker data in the joint-injury literature can provide insights into the pathogenesis and early risk trajectory related to PTOA and can help to elucidate a research agenda for preventing or slowing the onset of PTOA. Non-traumatic OA and PTOA have many clinical, radiological and genetic similarities, and efforts to understand early risk trajectories in PTOA might therefore contribute to the identification and classification of early non-traumatic OA, which is the most prevalent form of OA.

The prevalence of primary osteoarthritis is higher in females than males. However, it remains unclear if there are sex differences in the incidence of post-traumatic osteoarthritis after anterior cruciate ligament (ACL) reconstruction. In this study, we aimed to investigate the effects of sex on osteoarthritic changes after ACL reconstruction using an animal model. Rats were divided into the following four groups: male control, male ACL reconstruction, female control, and female ACL reconstruction. ACL reconstruction surgery was performed on the right knees of rats in the ACL reconstruction groups, while rats in the control groups did not undergo knee surgery. At 1, 4, and 12 weeks after surgery, cartilage degeneration in the medial tibial plateau and osteophyte formation in the proximal tibia were histologically assessed. After ACL reconstruction, an increase in the Mankin score, cartilage fissures, and osteophyte formation were detected within 12 weeks in both male and female rats, with similar degrees of these changes between males and females. However, changes in cartilage thickness and chondrocyte density after ACL reconstruction differed between males and females. Cartilage thickening was observed in male rats but not in female rats. The increase in chondrocyte density in the anterior region was detected in both males and females but was more pronounced in female rats. In conclusion, osteoarthritic changes were observed after ACL reconstruction in both male and female rats, but differences in changes in cartilage thickness and chondrocyte density were observed between males and females.