Xintong Xue, Changyi Li, Shuang Chen, Yan Zheng, Fan Zhang, Yan Xu
{"title":"17β-雌二醇通过调节FTO/IGF2BP1/m6A-NLRC5轴促进颞下颌关节骨关节炎的进展","authors":"Xintong Xue, Changyi Li, Shuang Chen, Yan Zheng, Fan Zhang, Yan Xu","doi":"10.1002/iid3.1361","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>E2 promoted the progression of TMJOA.</p>\n </section>\n </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295093/pdf/","citationCount":"0","resultStr":"{\"title\":\"17β-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis\",\"authors\":\"Xintong Xue, Changyi Li, Shuang Chen, Yan Zheng, Fan Zhang, Yan Xu\",\"doi\":\"10.1002/iid3.1361\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. 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17β-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis
Background
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms.
Methods
Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining.
Results
The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown.
期刊介绍:
Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including:
• cellular and molecular immunology
• clinical immunology
• allergy
• immunochemistry
• immunogenetics
• immune signalling
• immune development
• imaging
• mathematical modelling
• autoimmunity
• transplantation immunology
• cancer immunology