Background: Adipose stem cell–derived exosomes (ASC-Exos) are reported to effectively prevent muscle atrophy and degeneration of torn rat rotator cuff, but their influence on human samples and their potential mechanism are still unclear. Purpose: We aimed to investigate the effects of ASC-Exos on the metabolic activities of torn human rotator cuff tendons and explore the potential mechanism behind it. Study Design: Controlled laboratory study. Methods: Diseased supraspinatus tendons were harvested from 15 patients with a mean ± SD age of 65.8 ± 3.2 years who underwent reverse shoulder arthroplasty for chronic rotator cuff tears associated with glenohumeral pathological changes. Each tendon was dissected into 3 × 4 × 4–mm explants: the ones derived from the same tendon were placed into 12-well plates and cultured in complete culture media (control) or in complete culture media supplemented with ASC-Exos for 72 hours. Afterward, the concentrations of cytokines secreted into the culture media—including interleukin 1β (IL-1β), IL-6, IL-8, and matrix metalloproteinase 9 (MMP-9)—were measured using enzyme-linked immunosorbent assay (ELISA). Tendons were stained with hematoxylin and eosin and immunohistochemistry (type I and III collagens) for histological analyses. Moreover, the expression of anabolic genes ( TIMP-1 and TIMP-3; type I and III collagen encoding) and catabolic genes ( MMP-9 and MMP-13) in tendons were measured using real-time quantitative polymerase chain reaction. Phosphorylated AMPKα and Wnt/β-catenin pathways were assayed by western blotting to explore the potential mechanism of action of ASC-Exos. Results: Secretion of proinflammatory cytokines, including IL-1β, IL-6, and MMP-9, was significantly reduced in the ASC-Exos group as compared with the control group. Supraspinatus tendons in the ASC-Exos group exhibited superior histological properties, as demonstrated by higher tendon maturing scores and more type I collagen content, but there was no significant difference in type III collagen content between groups. Expression of MMP-9 and MMP-13 genes was decreased in the ASC-Exos group versus the control group. Increased expression of type I and III collagens and an elevated type I/III ratio were found in the ASC-Exos group when compared with the control group. There was no significant difference in the secretion of IL-8 and expression of TIMP-1 and TIMP-3 genes between the ASC-Exos and control groups. Western blotting revealed that ASC-Exos enhanced phosphorylated AMPKα and decreased β-catenin levels to prevent tendon degeneration. Conclusion: ASC-Exos maintained metabolic homeostasis of torn human rotator cuff tendons to improve their histological properties, which might be achieved by enhancing AMPK signaling to suppress Wnt/β-catenin activity. Clinical Relevance: ASC-Exos could be used as an effective biological tool to promote healing in torn human rotator cuff tendons.

Background Although the stenotic femoral intercondylar notch was associated with anterior cruciate ligament (ACL) injuries, the parameters for notch assessment were numerous. The present study aimed to compare the 2-dimensional (2D) femoral notch parameters, including the notch width (NW) and notch width index (NWI), with the 3-dimensional (3D) notch volume based on magnetic resonance imaging (MRI), to determine appropriate femoral parameters for ACL injuries. Methods Two hundred forty individuals were included in this study, including 120 patients with ACL ruptures and 120 age- and gender-matched individuals without ACL ruptures. The NWs and NWIs were measured at four sites (the popliteal groove, the notch inlet and outlet, and the ACL attachment), and the notch volumes were calculated. The Pearson correlation coefficients between the 2D and 3D parameters were calculated. A multivariate analysis of the ACL injuries was conducted with these parameters and the demographic data. Results The associations of the NW and NWI with the notch volume at each of the four locations of the femoral notch were poor in the subgroup analysis, with the exception of the NW in the male ACL-intact group (R = 0.307, 0.256, 0.404 and 0.387 at the popliteal groove, notch inlet and outlet, and ACL attachment, respectively). The multivariate analysis revealed that the notch volume (OR = 0.679, P < 0.001) and the NW at the popliteal groove (OR = 0.844, P = 0.004), notch inlet (OR = 0.720, P < 0.001) and ACL attachment (OR = 0.871, P = 0.028) were predictable parameters to the risk of ACL injuries. Conclusions The correlations between the 2D parameters and the 3D volumes were weak. The notch volume and the NW at the popliteal groove, notch inlet and ACL attachment were useful parameters for predicting the risk of ACL injuries. Level of evidence Level III, case-control study.

In Chinese Han adults, the notch volume was significantly smaller in the ACL-injured individuals than in the ACL-intact ones, it was smaller in females than the males and it was correlated with the body height, weight and the BMI. Level of evidence Level III, case-control study.