{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:47:23Z","timestamp":1787986043164,"version":"build-2784847793"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR072597"],"award-info":[{"award-number":["R01 AR072597"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR049069"],"award-info":[{"award-number":["R01 AR049069"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGF\u03b21 inducible cell model for human myofibroblastogenesis by both loss- and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle \u03b1-actin (ACTA2) at both mRNA and protein levels in basal and TGF\u03b21-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGF\u03b2-dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.<\/jats:p>","DOI":"10.3390\/jcm9113690","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T11:02:12Z","timestamp":1605610932000},"page":"3690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Potential Theragnostic Regulatory Axis for Arthrofibrosis Involving Adiponectin (ADIPOQ) Receptor 1 and 2 (ADIPOR1 and ADIPOR2), TGF\u03b21, and Smooth Muscle \u03b1-Actin (ACTA2)"],"prefix":"10.3390","volume":"9","author":[{"given":"Banu","family":"Bayram","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron R.","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Dudakovic","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Biochemistry &amp; Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Dagneaux","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis W.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob W.","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afton K.","family":"Limberg","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan E.","family":"Tibbo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Morrey","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Sanchez-Sotelo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0260-6773","authenticated-orcid":false,"given":"Jean-Pierre A.","family":"Kocher","sequence":"additional","affiliation":[{"name":"Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre J. van","family":"Wijnen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Biochemistry &amp; Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Abdel","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1016\/j.arth.2017.02.005","article-title":"Arthrofibrosis Associated with Total Knee Arthroplasty","volume":"32","author":"Cheuy","year":"2017","journal-title":"J. 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