{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:29:48Z","timestamp":1777577388300,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["81873997 and 82072426"],"award-info":[{"award-number":["81873997 and 82072426"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"natural science foundation of shanghai","doi-asserted-by":"publisher","award":["18ZR1428600"],"award-info":[{"award-number":["18ZR1428600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Adipose stem cell\u2013derived 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Controlled laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Diseased supraspinatus tendons were harvested from 15 patients with a mean \u00b1 SD age of 65.8 \u00b1 3.2 years who underwent reverse shoulder arthroplasty for chronic rotator cuff tears associated with glenohumeral pathological changes. Each tendon was dissected into 3 \u00d7 4 \u00d7 4\u2013mm 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\u2014including interleukin 1\u03b2 (IL-1\u03b2), IL-6, IL-8, and matrix metalloproteinase 9 (MMP-9)\u2014were 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 AMPK\u03b1 and Wnt\/\u03b2-catenin pathways were assayed by western blotting to explore the potential mechanism of action of ASC-Exos.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Secretion of proinflammatory cytokines, including IL-1\u03b2, 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 AMPK\u03b1 and decreased \u03b2-catenin levels to prevent tendon degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>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\/\u03b2-catenin activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>ASC-Exos could be used as an effective biological tool to promote healing in torn human rotator cuff tendons.<\/jats:p>\n                  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