{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T04:54:37Z","timestamp":1780808077757,"version":"3.54.1"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Synovial fibroblasts of rheumatoid arthritis (RA) play a critical role in perpetuation of chronic inflammation by interaction with immune and inflammatory cells and in cartilage and bone invasion, but current therapies for RA are not directly targeted fibroblasts. Selectively fibroblast targeted therapy has been hampered because of lack of fibroblast specific molecular signature. Recent advancement in technology enabled us to gain insightful information concerning RA synovial fibroblast subpopulations and functions. Exploring fibroblast targeted therapies have been focused on inducing cell death via fibroblast associated proteins; interrupting fibroblast binding to matrix protein; blocking intercellular signaling between fibroblasts and endothelial cells; inhibiting fibroblast proliferation and invasion; promoting cell apoptosis and inducing cellular senescence, and modulating fibroblast glucose metabolism. Translation into clinical studies of these fibroblast targeted strategies is required for evaluation for their clinical application, in particular for combination therapy with current immune component targeted therapies. Here, several strategies of fibroblast targeted therapy are highlighted.<\/jats:p>","DOI":"10.3389\/fmed.2022.846300","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T06:57:49Z","timestamp":1645081069000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Highlights of Strategies Targeting Fibroblasts for Novel Therapies for Rheumatoid Arthritis"],"prefix":"10.3389","volume":"9","author":[{"given":"Cong-Qiu","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers."},{"key":"B2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1083\/jcb.14.2.207","article-title":"Electron microscopy of the human synovial membrane","volume":"14","author":"Barland","year":"1962","journal-title":"J Cell Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/BF00270244","article-title":"Synovial lining cells","volume":"9","author":"Revell","year":"1989","journal-title":"Rheumatol Int."},{"key":"B4","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/art.40406","article-title":"The tumor-like phenotype of rheumatoid synovium: molecular profiling and prospects for precision medicine","volume":"70","author":"You","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0174-173X(83)80040-5","article-title":"Histomorphological basis of articular cartilage destruction in rheumatoid arthritis","volume":"3","author":"Fassbender","year":"1983","journal-title":"Coll Relat Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1038\/nm.2050","article-title":"Synovial fibroblasts spread rheumatoid arthritis to unaffected joints","volume":"15","author":"Lefevre","year":"2009","journal-title":"Nat Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0182751","DOI":"10.1371\/journal.pone.0182751","article-title":"Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis","volume":"12","author":"Choi","year":"2017","journal-title":"PLoS ONE."},{"key":"B8","doi-asserted-by":"publisher","first-page":"R90","DOI":"10.1186\/ar4555","article-title":"Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics","volume":"16","author":"Dennis","year":"2014","journal-title":"Arthritis Res Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.0105-2896.2009.00859.x","article-title":"Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis","volume":"233","author":"Bartok","year":"2010","journal-title":"Immunol Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.coph.2013.02.006","article-title":"The fibroblast as a therapeutic target in rheumatoid arthritis","volume":"13","author":"Filer","year":"2013","journal-title":"Curr Opin Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1126\/science.1139574","article-title":"Biomedicine. 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