Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation
Abstract Objectives Innate immunity plays a significant role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA), which is characterized by synovial inflammation and condylar cartilage degradation. We are urged to investigate the impact of Resatorvid, a preventative drug that inhib...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-03214-4 |
| _version_ | 1797414369124941824 |
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| author | Xin Liu Huimin Li Yaping Feng Huilin Guo Yingjie Li Jin Ke Xing Long |
| author_facet | Xin Liu Huimin Li Yaping Feng Huilin Guo Yingjie Li Jin Ke Xing Long |
| author_sort | Xin Liu |
| collection | DOAJ |
| description | Abstract Objectives Innate immunity plays a significant role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA), which is characterized by synovial inflammation and condylar cartilage degradation. We are urged to investigate the impact of Resatorvid, a preventative drug that inhibits Toll-like receptor 4 (TLR4), on experimental inflammatory TMJOA pathology. Methods An intra-articular injection of complete Freund’s adjuvant (CFA) was used to induce an experimental inflammatory mouse TMJOA model, and TLR4 expression was identified by immunofluorescent labeling. Intraperitoneal injections of Resatorvid were administered to CFA-induced TMJOA mice, and the pathology of TMJOA animals with and without Resatorvid treatment was examined by H&E, Safranin-O/Fast Green, and TRAP staining, as well as micro-CT, immunohistochemistry, and immunofluorescence. The impact of Resatorvid on chondrocyte pyroptosis and macrophage inflammation was further investigated using ATDC5 chondrocytes and RAW264.7 macrophages pretreated with relevant antagonists. Results CFA-induced TMJOA mice revealed remarkable synovial inflammation, together with a time course of cartilage degradation and bone destruction, with TLR4 elevated in the synovium and condylar cartilage. Prophylactic treatment with Resatorvid mitigated synovial inflammation, cartilage degeneration, and bone destruction in CFA-induced TMJOA mice and downregulated MyD88/NF-κB expression. Ex vivo studies demonstrated that Resatorvid treatment alleviated NOD-like receptor protein 3 (NLRP3)-mediated chondrocyte pyroptosis and degeneration and relieved macrophage inflammation by preventing reactive oxygen species (ROS) production through NLRP3 signaling. Conclusion Prophylactic treatment with Resatorvid alleviates TMJOA pathology by inhibiting chondrocyte pyroptosis and degeneration, as well as ROS-induced macrophage inflammation, through TLR4/MyD88/NF-κB/NLRP3. |
| first_indexed | 2024-03-09T05:32:05Z |
| format | Article |
| id | doaj.art-305785a3f9134636b738df8e81034e2b |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-09T05:32:05Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-305785a3f9134636b738df8e81034e2b2023-12-03T12:31:50ZengBMCArthritis Research & Therapy1478-63622023-11-0125111410.1186/s13075-023-03214-4Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammationXin Liu0Huimin Li1Yaping Feng2Huilin Guo3Yingjie Li4Jin Ke5Xing Long6State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan UniversityAbstract Objectives Innate immunity plays a significant role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA), which is characterized by synovial inflammation and condylar cartilage degradation. We are urged to investigate the impact of Resatorvid, a preventative drug that inhibits Toll-like receptor 4 (TLR4), on experimental inflammatory TMJOA pathology. Methods An intra-articular injection of complete Freund’s adjuvant (CFA) was used to induce an experimental inflammatory mouse TMJOA model, and TLR4 expression was identified by immunofluorescent labeling. Intraperitoneal injections of Resatorvid were administered to CFA-induced TMJOA mice, and the pathology of TMJOA animals with and without Resatorvid treatment was examined by H&E, Safranin-O/Fast Green, and TRAP staining, as well as micro-CT, immunohistochemistry, and immunofluorescence. The impact of Resatorvid on chondrocyte pyroptosis and macrophage inflammation was further investigated using ATDC5 chondrocytes and RAW264.7 macrophages pretreated with relevant antagonists. Results CFA-induced TMJOA mice revealed remarkable synovial inflammation, together with a time course of cartilage degradation and bone destruction, with TLR4 elevated in the synovium and condylar cartilage. Prophylactic treatment with Resatorvid mitigated synovial inflammation, cartilage degeneration, and bone destruction in CFA-induced TMJOA mice and downregulated MyD88/NF-κB expression. Ex vivo studies demonstrated that Resatorvid treatment alleviated NOD-like receptor protein 3 (NLRP3)-mediated chondrocyte pyroptosis and degeneration and relieved macrophage inflammation by preventing reactive oxygen species (ROS) production through NLRP3 signaling. Conclusion Prophylactic treatment with Resatorvid alleviates TMJOA pathology by inhibiting chondrocyte pyroptosis and degeneration, as well as ROS-induced macrophage inflammation, through TLR4/MyD88/NF-κB/NLRP3.https://doi.org/10.1186/s13075-023-03214-4TMJOAResatorvidChondrocyte pyroptosisMacrophage inflammationNLRP3ROS |
| spellingShingle | Xin Liu Huimin Li Yaping Feng Huilin Guo Yingjie Li Jin Ke Xing Long Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation Arthritis Research & Therapy TMJOA Resatorvid Chondrocyte pyroptosis Macrophage inflammation NLRP3 ROS |
| title | Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation |
| title_full | Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation |
| title_fullStr | Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation |
| title_full_unstemmed | Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation |
| title_short | Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation |
| title_sort | resatorvid alleviates experimental inflammatory tmjoa by restraining chondrocyte pyroptosis and synovial inflammation |
| topic | TMJOA Resatorvid Chondrocyte pyroptosis Macrophage inflammation NLRP3 ROS |
| url | https://doi.org/10.1186/s13075-023-03214-4 |
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