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In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund\u2019s complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young\u2019s modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-\u03baB) pathway occurs during the progression of TMJ arthritis. NF-\u03baB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-\u03baB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-\u03baB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.<\/jats:p>","DOI":"10.1038\/s41368-025-00352-0","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T07:14:58Z","timestamp":1744874098000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-\u03baB activation"],"prefix":"10.1038","volume":"17","author":[{"given":"Shengjie","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanning","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieni","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehua","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0447-5137","authenticated-orcid":false,"given":"Eileen","family":"Gentleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8193-6729","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"352_CR1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1177\/154411130301400207","volume":"14","author":"E Tanaka","year":"2003","unstructured":"Tanaka, E. & van Eijden, T. 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