{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:24:00Z","timestamp":1793658240321,"version":"4.5.1"},"reference-count":67,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013373","name":"National Institute for Health Research Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","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":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Tendons heal by fibrotic repair, increasing the likelihood of reinjury. Animal tendon injury and overuse models have identified transforming growth factor beta (TGF-\u03b2) and bone morphogenetic proteins (BMPs) as growth factors actively involved in the development of fibrosis, by mediating extracellular matrix synthesis and cell differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To understand how TGF-\u03b2 and BMPs contribute to fibrotic processes using tendon-derived cells isolated from healthy and diseased human tendons.<\/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>Tendon-derived cells were isolated from patients with a chronic rotator cuff tendon tear (large to massive, diseased) and healthy hamstring tendons of patients undergoing anterior cruciate ligament repair. Isolated cells were incubated with TGF-\u03b21 (10 ng\/mL) or BMP-2 (100 ng\/mL) for 3 days. Gene expression was measured by real-time quantitative polymerase chain reaction. Cell signaling pathway activation was determined by Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>TGF-\u03b21 treatment induced ACAN mRNA expression in both cell types but less in the diseased compared with healthy cells ( P &lt; .05). BMP-2 treatment induced BGN mRNA expression in healthy but not diseased cells ( P &lt; .01). In the diseased cells, TGF-\u03b21 treatment induced increased ACTA2 mRNA expression ( P &lt; .01) and increased small mothers against decapentaplegic (SMAD) signaling ( P &lt; .05) compared with those of healthy cells. Moreover, BMP-2 treatment induced ACTA2 mRNA expression in the diseased cells only ( P &lt; .05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Diseased tendon\u2013derived cells show reduced expression of the proteoglycans aggrecan and biglycan in response to TGF-\u03b21 and BMP-2 treatments. These same treatments induced enhanced fibrotic differentiation and canonical SMAD cell signaling in diseased compared with healthy cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>Findings from this study suggest that diseased tendon\u2013derived cells respond differently than healthy cells in the presence of TGF-\u03b21 and BMP-2. The altered responses of diseased cells may influence fibrotic repair processes during tendon healing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03635465211011158","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T21:49:18Z","timestamp":1622756958000},"page":"1892-1903","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparison of Cellular Responses to TGF-\u03b21 and BMP-2 Between Healthy and Torn Tendons"],"prefix":"10.1177","volume":"49","author":[{"given":"Wataru","family":"Morita","sequence":"first","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK"},{"name":"NIHR Oxford Biomedical Research Centre, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, 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