{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:10:30Z","timestamp":1787015430411,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570800"],"award-info":[{"award-number":["81570800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor \u03b21 (TGF\u2010\u03b21), bone morphogenetic proteins (eg BMP2) and type III TGF\u2010\u03b21 receptor (T\u03b2RIII) expression were markedly up\u2010regulated in AS\u2010SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF\u2010\u03b21, T\u03b2RIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS\u2010SL tissues. In vitro, AS\u2010SL fibroblasts (AS\u2010SLFs) showed high BMP2, TGF\u2010\u03b21 and T\u03b2RIII expression and auto\u2010osteogenic capacity. We further evaluated the role of T\u03b2RIII in the osteogenesis of normal SLFs. BMP2 combined with TGF\u2010\u03b21 induced the osteogenesis of T\u03b2RIII\u2010overexpressing SLFs, but the activity was lost in SLFs upon T\u03b2RIII knockdown. Moreover, our data suggested that BMP2 combined with TGF\u2010\u03b21 significantly activated both TGF\u2010\u03b21\/Smad signalling and BMP2\/Smad\/RUNX2 signalling to induce osteogenesis of SLFs with T\u03b2RIII up\u2010regulation. Furthermore, our multi\u2010strategy molecular interaction analysis approach indicated that TGF\u2010\u03b21 presented BMP2 to T\u03b2RIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of T\u03b2RIII\u2010overexpressing SLFs. Collectively, our results indicate that TGF\u2010\u03b21 combined with BMP2 may participate in the osteogenic differentiation of AS\u2010SLF by acting on up\u2010regulated T\u03b2RIII, resulting in excessive activation of both TGF\u2010\u03b21\/Smad and BMP2\/BMPR1A\/Smad\/RUNX2 signalling.<\/jats:p>","DOI":"10.1111\/jcmm.16262","type":"journal-article","created":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T23:37:22Z","timestamp":1610235442000},"page":"1613-1623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Up\u2010regulation of T\u03b2RIII facilitates the osteogenesis of supraspinous ligament\u2010derived fibroblasts from patients with ankylosing spondylitis"],"prefix":"10.1111","volume":"25","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Xinqiao Hospital Army Military Medical University Chongqing 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