{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:08:03Z","timestamp":1791378483370,"version":"4.3.2"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2003,12,8]],"date-time":"2003-12-08T00:00:00Z","timestamp":1070841600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Osteoarthritis (OA) is a joint disease characterized by osteophyte development, fibrosis, and articular cartilage damage. Effects of exogenous transforming growth factor \u03b2 (TGF\u03b2) isoforms and bone morphogenetic proteins (BMPs) suggest a role for these growth factors in the pathogenesis of OA. The aim of this study was to elucidate the role of endogenous TGF\u03b2 and BMP during papain\u2010induced OA\u2010like changes in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used adenoviral overexpression of TGF\u03b2 and BMP antagonists to block growth factor signaling. An adenovirus expressing a secreted, pan\u2013specific TGF\u03b2 antagonist called murine latency\u2010associated peptide 1 (mLAP\u20101) was used. In addition, we used intracellular inhibitory Smad6 as a BMP antagonist and Smad7 as a TGF\u03b2\/BMP inhibitor. Papain was injected into the knee joints of C57BL\/6 mice to induce osteophyte development, synovial thickening, and articular cartilage proteoglycan (PG) loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intraarticular injection of papain caused increased protein expression of several TGF\u03b2 and BMP isoforms in synovium and cartilage. Adenovirus transfection into the joint resulted in a strong expression of the transgenes in the synovial lining. Overexpression of mLAP\u20101, Smad6, and Smad7 led to a significant reduction in osteophyte formation compared with that in controls. Smad6 and Smad7 overexpression also significantly decreased synovial thickening. Furthermore, the secreted TGF\u03b2 inhibitor mLAP\u20101 increased articular cartilage PG loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate a pivotal role of endogenous TGF\u03b2 in the development of osteophytes and synovial thickening, implicating endogenous TGF\u03b2 in the pathogenesis of OA. In contrast, the prevention of cartilage damage by endogenous TGF\u03b2 signifies the protective role of TGF\u03b2 in articular cartilage. This is the first study to demonstrate that endogenous BMPs are involved in osteophyte formation and synovial thickening in experimental OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.11328","type":"journal-article","created":{"date-parts":[[2003,12,9]],"date-time":"2003-12-09T09:00:36Z","timestamp":1070960436000},"page":"3442-3451","source":"Crossref","is-referenced-by-count":165,"title":["Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor \u03b2\/bone morphogenetic protein inhibitors during experimental osteoarthritis"],"prefix":"10.1002","volume":"48","author":[{"given":"Alwin","family":"Scharstuhl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elly L.","family":"Vitters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van der 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