Tendon injuries are common musculoskeletal system disorders in clinical, but the regeneration ability of tendon is limited. Tendon stem cells (TSCs) have shown promising effect on tissue engineering and been used for the treatment of tendon injury. Exosomes that serve as genetic information carriers have been implicated in many diseases and physiological processes, but effect of exosomes from TSCs on tendon injury repair is unclear. The aim of this study is to make clear that the effect of exosomes from TSCs on tendon injury healing. Exosomes were harvested from conditioned culture media of TSCs by a sequential centrifugation process. Rat Achilles tendon tendinopathy model was established by collagenase‐I injection. This was followed by intra‐Achilles‐tendon injection with TSCs or exosomes. Tendon healing and matrix degradation were evaluated by histology analysis and biomechanical test at the post‐injury 5 weeks. In vitro, TSCs treated with interleukin 1 beta were added by conditioned medium including exosomes or not, or by exosomes or not. Tendon matrix related markers and tenogenesis related markers were measured by immunostaining and western blot. We found that TSCs injection and exosomes injection significantly decreased matrix metalloproteinases (MMP)‐3 expression, increased expression of tissue inhibitor of metalloproteinase‐3 (TIMP‐3) and Col‐1a1, and increased biomechanical properties of the ultimate stress and maximum loading. In vitro, conditioned medium with exosomes and exosomes also significantly decreased MMP‐3, and increased expression of tenomodulin, Col‐1a1 and TIMP‐3. Exosomes from TSCs could be an ideal therapeutic strategy in tendon injury healing for its balancing tendon extracellular matrix and promoting the tenogenesis of TSCs.

Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.

Objectively: Tendinopathy is a common problem in sports medicine which can lead to severe morbidity. Aspirin, as the classical representative of non‐steroidal anti‐inflammatory drugs (NSAIDs) for its anti‐inflammatory and analgesic actions, has been commonly used in treating tendinopathy. While its treatment effects on injury tendon healing are lacking, illuminating the underlying mechanism may provide scientific basis for clinical treatment.Materials and methods: Firstly, we used immunohistochemistry and qRT‐PCR to detect changes in CD14, CD206, iNOS, IL‐6, IL‐10, MMP‐3, TIMP‐3, Col‐1a1, biglycan, Comp, Fibronectin, TGF‐β1，ACAN，EGR‐1 and FMOD. Next, Western blot was used to measure the protein levels (IL‐6, IL‐10, TGF‐β1, COMP, TIMP‐3, STAT‐3/P‐STAT‐3 and JNK/P‐JNK) in TSCs. Then, migration and proliferation of TSCs were measured through wound healing test and BrdU staining. Finally, the mechanical properties of injury tendon were detected.Results: After aspirin treatment, the inflammation and scar formation in injury tendon were significantly inhibited by aspirin. Still, tendon's ECM was positively balanced. Increasing migration and proliferation ability of TSCs induced by IL‐1β were significantly reversed. JNK/STAT‐3 signalling pathway participated in the process above. In addition, biomechanical properties of injury tendon were significantly improved.Conclusions: Taken together, the findings suggested that aspirin inhibited inflammation and scar formation via regulation of JNK/STAT‐3 signalling and decreased rerupture risk of injury tendon. Aspirin could be an ideal therapeutic strategy in tendon injury healing.

BACKGROUND:Inflammation after tendon-bone junction injury results in the formation of excessive scar tissue and poor biomechanical properties. Recent research has shown that exosomes derived from bone marrow stromal cells (BMSCs) can modulate inflammation during tissue healing. Thus, our study aimed to enhance tendon-bone healing by use of BMSC-derived exosomes (BMSC-Exos). MATERIAL AND METHODS:The mouse tendon-bone reconstruction model was established, and the mice were randomly divided into 3 groups: the control group, the hydrogel group, and the hydrogel+exosome group, with 30 mice in each group. At 7 days, 14 days, and 1 month after surgery, tendon-bone junction samples were harvested, and the macrophage polarization and tendon-bone healing were evaluated based on histology, immunofluorescence, and quantitative RT-PCR (qRT-PCR) analysis. RESULTS:In the early phase, we observed significantly higher numbers of M2 macrophages and more anti-inflammatory and chondrogenic-related factors in the hydrogel+BMSC-Exos group compared with the control group and the hydrogel group. The M1 macrophages and related proinflammatory factors decreased. Cell apoptosis decreased in the hydrogel+BMSC-Exos group, while cell proliferation increased; in particular, the CD146+ stem cells substantially increased. At 1 month after surgery, there was more fibrocartilage in the hydrogel+BMSC-Exos group than in the other groups. Biomechanical testing showed that the maximum force, strength, and elastic modulus were significantly improved in the hydrogel+BMSC-Exos group. CONCLUSIONS:Our study provides evidence that the local administration of BMSC-Exos promotes the formation of fibrocartilage by increasing M2 macrophage polarization in tendon-to-bone healing, leading to improved biomechanical properties. These findings provide a basis for the potential clinical use of BMSC-Exos in tendon-bone repair.

Background: The surgical management of chronic lateral ankle instability (CLAI) has evolved since the 1930s, but for the past 50 years, the modified Broström technique of ligament repair has been the gold standard. However, with the development of arthroscopic techniques, significant variation remains regarding when and how CLAI is treated operatively, which graft is the optimal choice, and which other controversial factors should be considered. Purpose: To develop clinical guidelines on the surgical treatment of CLAI and provide standardized guidelines for indications, surgical techniques, rehabilitation strategies, and assessment measures for patients with CLAI. Study Design: A consensus statement of the Chinese Society of Sports Medicine. Methods: A total of 14 physicians were queried for their input on guidelines for the surgical management of CLAI. After 9 clinical topics were proposed, a comprehensive systematic search of the literature published since 1980 was performed for each topic through use of China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, EMBASE, and the Cochrane Library. The recommendations and statements were drafted, discussed, and finalized by all authors. The recommendations were graded as grade 1 (strong) or 2 (weak) based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) concept. Based on the input from 28 external specialists independent from the authors, the clinical guidelines were modified and finalized. Results: A total of 9 topics were covered with regard to the following clinical areas: surgical indications, surgical techniques, whether to address intra-articular lesions, rehabilitation strategies, and assessments. Among the 9 topics, 6 recommendations were rated as strong and 3 recommendations were rated as weak. Each topic included a statement about how the recommendation was graded. Conclusion: This guideline provides recommendations for the surgical management of CLAI based on the evidence. We believe that this guideline will provide a useful tool for physicians in the decision-making process for the surgical treatment of patients with CLAI.