{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:41:05Z","timestamp":1788925265294,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti\u2010fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGF\u03b21\u2010mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGF\u03b21\u2010induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA\u2010seq analysis corroborated the anti\u2010myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25\u2009mg\/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle\u2010treated mice, 5\u2009mg\/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.<\/jats:p>","DOI":"10.1002\/jcp.31168","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T13:09:21Z","timestamp":1703682561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["AdipoRon reduces TGF\u03b21\u2010mediated collagen deposition in vitro and alleviates knee stiffness in vivo"],"prefix":"10.1002","volume":"239","author":[{"given":"Amel","family":"Dudakovic","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic Rochester Minnesota USA"},{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afton K.","family":"Limberg","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic Rochester Minnesota 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