{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:27:52Z","timestamp":1790836072416,"version":"4.1.0"},"reference-count":76,"publisher":"American Society for Clinical Investigation","issue":"3","funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["1BX002337A"],"award-info":[{"award-number":["1BX002337A"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21EB019509"],"award-info":[{"award-number":["R21EB019509"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R01 GM118300-01"],"award-info":[{"award-number":["1R01 GM118300-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009663","name":"University Health Network","doi-asserted-by":"crossref","award":["The Campaign to Cure Arthritis"],"award-info":[{"award-number":["The Campaign to Cure Arthritis"]}],"id":[{"id":"10.13039\/100009663","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,8]]},"abstract":"<jats:p>\n                    Osteoarthritis (OA) is a degenerative joint disease involving both cartilage and synovium. The canonical Wnt\/\u03b2-catenin pathway, which is activated in OA, is emerging as an important regulator of tissue repair and fibrosis. This study seeks to examine Wnt pathway effects on synovial fibroblasts and articular chondrocytes as well as the therapeutic effects of Wnt inhibition on OA disease severity. Mice underwent destabilization of the medial meniscus surgery and were treated by intra-articular injection with XAV-939, a small-molecule inhibitor of Wnt\/\u03b2-catenin signaling. Wnt\/\u03b2-catenin signaling was highly activated in murine synovial fibroblasts as well as in OA-derived human synovial fibroblasts. XAV-939 ameliorated OA severity associated with reduced cartilage degeneration and synovitis in vivo. Wnt inhibition using mechanistically distinct small-molecule inhibitors, XAV-939 and C113, attenuated the proliferation and type I collagen synthesis in synovial fibroblasts in vitro but did not affect human OA-derived chondrocyte proliferation. However, Wnt modulation increased\n                    <jats:italic>COL2A1<\/jats:italic>\n                    and\n                    <jats:italic>PRG4<\/jats:italic>\n                    transcripts, which are downregulated in chondrocytes in OA. In conclusion, therapeutic Wnt inhibition reduced disease severity in a model of traumatic OA via promoting anticatabolic effects on chondrocytes and antifibrotic effects on synovial fibroblasts and may be a promising class of drugs for the treatment of OA.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.96308","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T11:01:03Z","timestamp":1518001263000},"source":"Crossref","is-referenced-by-count":167,"title":["Inhibition of Wnt\/\u03b2-catenin signaling ameliorates osteoarthritis in a murine model of experimental osteoarthritis"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-2751","authenticated-orcid":true,"given":"Caressa","family":"Lietman","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, 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