{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T03:28:15Z","timestamp":1774668495193,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T00:00:00Z","timestamp":1588377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004398","name":"Mitsubishi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"\n Objective<\/jats:title>\n \n We have previously reported that the coactivation of\n NF<\/jats:styled-content>\n \u2010\u03baB and\n STAT<\/jats:styled-content>\n 3 in nonimmune cells, including synovial fibroblasts, enhances the expression of\n NF<\/jats:styled-content>\n \u2010\u03baB target genes and plays a role in chronic inflammation and rheumatoid arthritis (\n RA<\/jats:styled-content>\n ). This study was undertaken to examine the role of\n NF<\/jats:styled-content>\n \u2010\u03baB activation in chondrocytes and better understand the pathogenesis of\n RA<\/jats:styled-content>\n . Furthermore, transmembrane protein 147 (\n TMEM<\/jats:styled-content>\n 147) was investigated as a representative\n NF<\/jats:styled-content>\n \u2010\u03baB activator in chondrocytes.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Clinical samples from\n RA<\/jats:styled-content>\n patients were analyzed by immunohistochemistry. Specimens obtained from patients with polydactyly were used as control samples. The functional contribution of chondrocytes and\n TMEM<\/jats:styled-content>\n 147 to arthritis was examined in several murine models of\n RA<\/jats:styled-content>\n . In vitro experiments (quantitative polymerase chain reaction,\n RNA<\/jats:styled-content>\n interference, immunoprecipitation, and confocal microscopy) were performed to investigate the mechanism of action of\n TMEM<\/jats:styled-content>\n 147 in chondrocytes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Samples obtained from\n RA<\/jats:styled-content>\n patients and mouse models of RA showed coactivation of\n NF<\/jats:styled-content>\n \u2010\u03baB and\n STAT<\/jats:styled-content>\n 3 in chondrocytes (\n P<\/jats:italic>\n < 0.001). This coactivation induced a synergistic expression of\n NF<\/jats:styled-content>\n \u2010\u03baB targets in vitro (\n P<\/jats:italic>\n < 0.01). Chondrocyte\u2010specific deletion of\n STAT<\/jats:styled-content>\n 3 significantly suppressed the development of cytokine\u2010induced\n RA<\/jats:styled-content>\n (\n P<\/jats:italic>\n < 0.01).\n TMEM<\/jats:styled-content>\n 147 was highly expressed in chondrocytes from\n RA<\/jats:styled-content>\n patient samples and the mouse models of RA. Gene silencing of\n TMEM<\/jats:styled-content>\n 147 or anti\u2010\n TMEM<\/jats:styled-content>\n 147 antibody treatment inhibited the cytokine\u2010mediated activation of\n NF<\/jats:styled-content>\n \u2010\u03baB in vitro (\n P<\/jats:italic>\n < 0.01) and suppressed cytokine\u2010induced\n RA<\/jats:styled-content>\n in vivo (\n P<\/jats:italic>\n < 0.01). Mechanistically,\n TMEM<\/jats:styled-content>\n 147 molecules acted as scaffold proteins for the\n NF<\/jats:styled-content>\n \u2010\u03baB complex, which included breakpoint cluster region and casein kinase 2, and enhanced\n NF<\/jats:styled-content>\n \u2010\u03baB activity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These results suggest that chondrocytes play a role in the development of\n RA<\/jats:styled-content>\n via\n TMEM<\/jats:styled-content>\n 147\u2010mediated\n NF<\/jats:styled-content>\n \u2010\u03baB activation and indicate a novel therapeutic strategy for\n RA<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.41182","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T05:05:27Z","timestamp":1575263127000},"page":"931-942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147\u2013Mediated\n NF<\/scp>\n \u2010\u03baB Activation"],"prefix":"10.1002","volume":"72","author":[{"given":"Mitsutoshi","family":"Ota","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Institute of Genetic Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuma","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido 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