These results identify a novel strategy for AC remediation via small molecule-mediated modulation of gp130 signalling.

Objective Articular cartilage is a highly specialized tissue which forms the surfaces in synovial joints. Full-thickness cartilage defects caused by trauma or microfracture surgery heal via the formation of fibrotic tissue characterized by a high content of collagen I (COL I) and subsequent poor mechanical properties. The goal of this study is to investigate the molecular mechanisms underlying fibrosis after joint injury. Design Rat knee joint models are used to mimic cartilage defects after acute injury. Immunohistochemistry was performed to detect proteins related to fibrosis. Human fetal chondroyges and bone marrow stromal cells (BMSCs) were used to study the influence of lipid lysophosphatidic acid (LPA) on Collagen I (COL I) synthesis. Quantitative PCR, ELISA and immunohistochemistry were performed to evaluate the productions of COL I. Chemical inhibitors were used to block LPA signaling both in vitro and in vivo. Results After full-thickness cartilage injury in rat knee joints, stromal cells migrating to the injury expressed high levels of the LPA-producing enzyme autotaxin (ATX); intact articular cartilage in rat and humans expressed negligible levels of ATX despite expressing the LPA receptors LPAR1 and LPAR2. LPA-induced increases in COL I production by chondrocytes and BMSCs was mediated via the MAP kinase (MAPK) and PI3 Kinase (PI3K) signaling pathways. Inhibition of the ATX/LPA axis significantly reduced COL I-enriched fibrocartilage synthesis in full-thickness cartilage defects in rats in favor of the collagen II-enriched normal state. Conclusion Taken together, these results identify an attractive target for intervention in reducing the progression of post-traumatic osteoarthritis.

» The prevalence of ulnar collateral ligament (UCL) injury and UCL reconstruction (UCL-R) continues to rise, causing morbidity in overhead-throwing athletes.» Postoperative rehabilitation protocols are essential for proper healing of the reconstructed ligament and safely returning athletes to competition, yet there is no uniformly accepted standard of care.» UCL-R rehabilitation has traditionally been guided by expert opinion and conventional wisdom rather than scientific studies, resulting in substantial variability in rehabilitation practices, time to return to play, and outcomes.» Current research efforts aim to closely investigate the biomechanical implications of UCL-R and overhead throwing to better guide rehabilitation and to improve competitive performance and outcomes.» Additional biomechanical and scientific studies on rehabilitation modalities and timing are warranted for systematic analysis, optimization, and standardization of UCL-R rehabilitation.

Athletes participating in overhead sports are at particularly high risk of shoulder impingement syndrome. Subcoracoid impingement is defined as impingement of the anterior soft tissues of the shoulder between the coracoid process and the lesser tuberosity. Subacromial impingement syndrome (SIS) occurs due to extrinsic compression of the rotator cuff between the humeral head and coracoacromial structures or intrinsic degeneration of the supraspinatus tendon and subsequent superior migration of the humerus. Internal impingement is a major cause of shoulder pain in overhead athletes, and it occurs due to repetitive impingement of the articular surface of the rotator cuff with the glenoid during maximum abduction and external rotation of the arm. When examining athletes with suspected impingement of the shoulder, it is important to discuss the sport-specific motion that regenerates the symptoms and perform a combination of physical examination tests to improve the diagnostic accuracy. Radiographic evaluation is recommended, and the extent of soft tissue abnormalities can be assessed on ultrasound or magnetic resonance imaging of the shoulder. Management of shoulder impingement syndrome can be conservative or operative, based on the severity and chronicity of symptoms and the associated structural abnormalities. This review provides an update on the management of SIS, subcoracoid impingement, and internal impingement in the athletic population.

Objective:To comprehensively review and report the outcomes of ankle syndesmotic injury management in elite athletes.Data sources:Three databases were searched for articles reporting the rate of return to sport following treatment of ankle syndesmotic injuries in elite athletes (collegiate or professional level). Ten articles and 440 athletes were included. Articles reporting the rate of return to sport following high ankle sprain injury in elite athletes. Data collected included demographics, type of treatment received, and return to sport (RTS) information. A random effects model was used.Main results:The estimated overall rate of RTS was 99% (95% CI, 95.5-99.9). The mean time to RTS was 38 ± 18 (range, 14-137) days. Of the 440 athletes, 269 (269/440%, 61%) were treated nonoperatively (nonoperative group); the rate of RTS was 99.6%, and the athletes returned at a mean time of 29 ± 14 (range, 13-45) days. A total of 171 athletes (171 of 440%, 39%) underwent surgical treatment (operative group). All (171 of 171%, 100%) athletes returned at a mean time of 50.3 ± 13 (range, 41-137) days. Almost all athletes who underwent surgery had suture button fixation (164 of 171 athletes, 96%), and the mean time to RTS was 7 weeks with 9.1% complication rate.Conclusions:Elite athletes with ankle syndesmosis injury return to sport at an extremely high rates, following operative or nonoperative treatment. Return to the preinjury level of competition should be expected at 4 weeks and 7 weeks in high-level athletes who undergo nonoperative and operative management, respectively. Suture button fixation was used by the majority of studies reporting surgical management of ankle syndesmosis injuries in athletes.

Knee fibrosis is characterized by the presence of excessive connective tissue due to dysregulated fibroblast activation following local or systemic tissue damage. Knee fibrosis constitutes a major clinical problem in orthopaedics due to the severe limitation in the knee range of motion that leads to compromised function and patient disability. Knee osteoarthritis is an extremely common orthopedic condition that is associated with patient disability and major costs to the health-care systems worldwide. Although knee fibrosis and osteoarthritis (OA) have traditionally been perceived as two separate pathologic entities, recent research has shown common ground between the pathophysiologic processes that lead to the development of these two conditions. The purpose of this review was to identify the pathophysiologic pathways as well as key molecules that are implicated in the development of both knee OA and knee fibrosis in order to understand the relationship between the two diagnoses and potentially identify novel therapeutic targets.

Osteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.

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