Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation
Abstract Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alteratio...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-025-00352-0 |
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| author | Shengjie Cui Yanning Guo Yu Fu Ting Zhang Jieni Zhang Yehua Gan Yanheng Zhou Yan Gu Eileen Gentleman Yan Liu Xuedong Wang |
| author_facet | Shengjie Cui Yanning Guo Yu Fu Ting Zhang Jieni Zhang Yehua Gan Yanheng Zhou Yan Gu Eileen Gentleman Yan Liu Xuedong Wang |
| author_sort | Shengjie Cui |
| collection | DOAJ |
| description | Abstract Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. 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’s 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’s modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement. |
| format | Article |
| id | doaj-art-1ef679ad94464b219bf2b20fa140daa5 |
| institution | OA Journals |
| issn | 2049-3169 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj-art-1ef679ad94464b219bf2b20fa140daa52025-08-20T02:24:26ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-04-0117111210.1038/s41368-025-00352-0Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activationShengjie Cui0Yanning Guo1Yu Fu2Ting Zhang3Jieni Zhang4Yehua Gan5Yanheng Zhou6Yan Gu7Eileen Gentleman8Yan Liu9Xuedong Wang10Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsFourth Clinical Division, Peking University School and Hospital of StomatologyDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsCenter for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of StomatologyDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsCentre for Craniofacial and Regenerative Biology, King’s College LondonDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsDepartment of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental MaterialsAbstract Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. 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’s 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’s modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.https://doi.org/10.1038/s41368-025-00352-0 |
| spellingShingle | Shengjie Cui Yanning Guo Yu Fu Ting Zhang Jieni Zhang Yehua Gan Yanheng Zhou Yan Gu Eileen Gentleman Yan Liu Xuedong Wang Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation International Journal of Oral Science |
| title | Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation |
| title_full | Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation |
| title_fullStr | Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation |
| title_full_unstemmed | Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation |
| title_short | Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation |
| title_sort | inflammation related collagen fibril destruction contributes to temporomandibular joint disc displacement via nf κb activation |
| url | https://doi.org/10.1038/s41368-025-00352-0 |
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