{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:31:49Z","timestamp":1791487909116,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2007,11,29]],"date-time":"2007-11-29T00:00:00Z","timestamp":1196294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Ligands and antagonists of the WNT pathway are linked to osteoporosis and osteoarthritis. In particular, polymorphisms in the <jats:italic>FRZB<\/jats:italic> gene, a secreted WNT antagonist, have been associated with osteoarthritis. The aim of this study was to examine cartilage and bone in Frzb<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>Frzb<\/jats:italic> gene in mice was inactivated using a Cre\/loxP strategy. Three models of osteoarthritis were used: collagenase, papain, and methylated bovine serum albumin induced. Bone biology was studied using density measurements and microfocal computed tomography. Bone stiffness and mechanical loading\u2013induced bone adaptation were studied by compression of the ulnae.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Targeted deletion of the <jats:italic>Frzb<\/jats:italic> gene in mice increased articular cartilage loss during arthritis triggered by instability, enzymatic injury, or inflammation. Cartilage damage in Frzb<jats:sup>\u2212\/\u2212<\/jats:sup> mice was associated with increased WNT signaling and matrix metalloproteinase 3 (MMP\u20103) expression and activity. Frzb<jats:sup>\u2212\/\u2212<\/jats:sup> mice had increased cortical bone thickness and density, resulting in stiffer bones, as demonstrated by stress\u2013strain relationship analyses. Moreover, Frzb<jats:sup>\u2212\/\u2212<\/jats:sup> mice had an increased periosteal anabolic response to mechanical loading as compared with wild\u2010type mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The genetic association between osteoarthritis and <jats:italic>FRZB<\/jats:italic> polymorphisms is corroborated by increased cartilage proteoglycan loss in 3 different models of arthritis in Frzb<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Loss of <jats:italic>Frzb<\/jats:italic> may contribute to cartilage damage by increasing the expression and activity of MMPs, in a WNT\u2010dependent and WNT\u2010independent manner. FRZB deficiency also resulted in thicker cortical bone, with increased stiffness and higher cortical appositional bone formation after loading. This may contribute to the development of osteoarthritis by producing increased strain on the articular cartilage during normal locomotion but may protect against osteoporotic fractures.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23137","type":"journal-article","created":{"date-parts":[[2007,11,29]],"date-time":"2007-11-29T17:17:04Z","timestamp":1196356624000},"page":"4095-4103","source":"Crossref","is-referenced-by-count":245,"title":["Articular cartilage and biomechanical properties of the long bones in <i>Frzb<\/i>\u2010knockout mice"],"prefix":"10.1002","volume":"56","author":[{"given":"Rik J. 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