{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:56:48Z","timestamp":1791838608918,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasties (TKAs). Currently, treatment options are limited. Therefore, an in vitro model of knee\u2010related myofibroblastogenesis is valuable to facilitate investigation of the arthrofibrotic process, diagnostic and therapeutic options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissues from the knees of four patients undergoing primary TKAs for osteoarthritis. From these tissues, we isolated primary cells by the outgrowth method and subsequently characterized these cells in the absence and presence of the pro\u2010myofibroblastic cytokine, transforming growth factor beta 1 (TGF\u03b21). Light microscopy of knee outgrowth cells revealed spindle\u2010shaped cells, and immunofluorescence (IF) analysis demonstrated staining for the fibroblast\u2010specific markers TE\u20107 and vimentin (VIM). These knee outgrowth fibroblasts differentiated readily into myofibroblasts as reflected by enhanced \u03b1\u2010smooth muscle actin (<jats:italic>ACTA2<\/jats:italic>) mRNA and protein expression and increased mRNA expression of collagen type 1 (<jats:italic>COL1A1<\/jats:italic>) and type 3 (<jats:italic>COL3A1<\/jats:italic>) with collagenous matrix deposition in the presence of TGF\u03b21. Outgrowth knee fibroblasts were more sensitive to TGF\u03b21\u2010mediated myofibroblastogenesis than adipose\u2010derived mesenchymal stromal\/stem cells (MSCs). While outgrowth knee fibroblasts isolated from three anatomical regions in four patients exhibited similar gene expression, these cells are distinct from other fibroblastic cell types (i.e., Dupuytren's fibroblasts) as revealed by RNA\u2010sequencing. In conclusion, our study provides an in vitro myofibroblastic model of outgrowth knee fibroblasts derived from patients undergoing primary TKA that can be utilized to study myofibroblastogenesis and assess therapeutic strategies for arthrofibrosis.<\/jats:p>","DOI":"10.1002\/jcb.30230","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T08:24:58Z","timestamp":1646036698000},"page":"878-892","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGF\u03b21 stimulation"],"prefix":"10.1002","volume":"123","author":[{"given":"Banu","family":"Bayram","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic  Rochester Minnesota 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