{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:11:30Z","timestamp":1794003090483,"version":"4.8.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2020YJ0045"],"award-info":[{"award-number":["2020YJ0045"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771097"],"award-info":[{"award-number":["81771097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800928"],"award-info":[{"award-number":["81800928"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801003"],"award-info":[{"award-number":["81801003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071139"],"award-info":[{"award-number":["82071139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:p>\n                    In this study, we investigate harnessing fibrocartilage stem cell (FCSC) capacities by regulating tumor necrosis factor \u03b1 (TNF-\u03b1) signaling for cartilage repair in temporomandibular joint osteoarthritis (TMJOA). Stem cell specifics for FCSCs were characterized in the presence of TNF-\u03b1. Etanercept as a TNF-\u03b1 inhibitor and BAY 11-7082 as an Nf-\u03baB inhibitor were used to study TNF-\u03b1 regulation of FCSCs. Lineage tracing was performed in Gli1-CreERT\n                    <jats:sup>+<\/jats:sup>\n                    ;Tm\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice when etanercept (1\u2009mg\/kg, every 3\u2009d) or isometric vehicle was subcutaneously injected to trace specific changes in FCSCs. Surgically induced TMJOA Sprague-Dawley rats were generated with BAY 11-7082 (5\u2009mg\/kg, every 3\u2009d) or vehicle subcutaneous injection to investigate the functional role of TNF-\u03b1\/Nf-\u03baB in TMJOA. Anterior disc displacement (ADD) rabbits were used to analyze the therapeutic effect of etanercept as a TMJOA intra-articular treatment with etanercept (0.02\u2009mg in 100\u2009\u03bcL, every 2\u2009wk) or isometric vehicle. In vitro, TNF-\u03b1 inhibited proliferation of FCSCs and increased FCSC apoptosis. TNF-\u03b1 activation interfered with osteogenic and chondrogenic differentiation of FCSCs, while etanercept could partially recover FCSC specificity from TNF-\u03b1. FCSC lineage tracing in Gli1-CreERT\n                    <jats:sup>+<\/jats:sup>\n                    ;Tm\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice showed that the chondrogenic capacity of Gli1\n                    <jats:sup>+<\/jats:sup>\n                    cell lineage was markedly suppressed in osteoarthritis cartilage, the phenotype of which could be significantly rescued by etanercept. Specifically blocking the Nf-\u03baB pathway could significantly weaken the regulatory effect of TNF-\u03b1 on FCSC specificity in vitro and in TMJOA rats in vivo. Finally, intra-articular etanercept treatment efficiently rescued TMJ cartilage degeneration and growth retardation in ADD rabbits. Inhibition of TNF-\u03b1 signaling reduced Nf-\u03baB transcripts and recovered FCSC specificities. In vivo, etanercept treatment effectively rescued the osteoarthritis phenotype in TMJOA mice and ADD rabbits. These data suggest a novel therapeutic mechanism whereby TNF-\u03b1\/Nf-\u03baB inhibition promotes FCSC chondrogenic capacity for cartilage transformation in TMJOA.\n                  <\/jats:p>","DOI":"10.1177\/00220345211037248","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T09:43:23Z","timestamp":1631526203000},"page":"312-322","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Regulating Fibrocartilage Stem Cells via TNF-\u03b1\/Nf-\u03baB in TMJ Osteoarthritis"],"prefix":"10.1177","volume":"101","author":[{"given":"R.","family":"Bi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 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