{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:13:15Z","timestamp":1785391995431,"version":"3.55.0"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The CCN family of matricellular proteins (CYR61\/CCN1, CTGF\/CCN2, NOV\/CCN3 and WISP1-2-3\/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.<\/jats:p>","DOI":"10.3390\/ijms22094340","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"4340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis"],"prefix":"10.3390","volume":"22","author":[{"given":"Iona J.","family":"MacDonald","sequence":"first","affiliation":[{"name":"Graduate Institute of Basic Medical Science, Collage of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3445-4353","authenticated-orcid":false,"given":"Chien-Chung","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Collage of Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung 404332, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Chi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 65152, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-1115","authenticated-orcid":false,"given":"Yen-You","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science, Collage of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-8352","authenticated-orcid":false,"given":"Chih-Hsin","family":"Tang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medical Science, Collage of Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"School of Medicine, Collage of Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, Collage of Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Chinese Medicine Research Center, China Medical University, Taichung 406040, Taiwan"},{"name":"Department of Biotechnology, College of Health Science, Asia University, Taichung 413305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","unstructured":"Senthelal, S., Li, J., Goyal, A., Bansal, P., and Thomas, M.A. (2021). 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