{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:56:49Z","timestamp":1779911809956,"version":"3.53.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T00:00:00Z","timestamp":1188432000000},"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":[[2007,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The biologic changes associated with osteoarthritis (OA) are incompletely understood. The aim of this study was to elucidate the molecular mechanisms underlying OA progression in an STR\/Ort murine model of spontaneous disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Global patterns of gene expression were assessed using microarray analysis of articular cartilage\/subchondral bone from the tibial plateaus of STR\/Ort mice at 3, 9, and 12 months of age. The age\u2010dependent severity of osteophyte formation and extent of cartilage damage were determined in the corresponding femurs using microfocal computed tomography and the Mankin histologic scoring system. Pathway analysis was used to identify the functions of genes associated with OA progression, and changes in gene expression were confirmed using immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six hundred twenty\u2010one genes were associated with both osteophyte formation and cartilage damage in the STR\/Ort joints. Genes involved in the development\/function of connective tissue and in lipid metabolism were most significantly enriched and regulated during disease progression. Genes directly interacting with peroxisome proliferator\u2013activated receptor \u03b1 (PPAR\u03b1)\/PPAR\u03b3 were down\u2010regulated, whereas those genes involved with connective tissue remodeling were up\u2010regulated during disease progression. Associations of down\u2010regulation of myotubularin\u2010related phosphatase 1 (a phosphoinositide 3\u2010phosphatase involved in lipid signaling) and up\u2010regulation of biglycan (a member of the small leucine\u2010rich protein family known to modulate osteoblast differentiation and matrix mineralization) with OA progression were confirmed by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Since adipogenesis and osteogenesis are inversely related in the developing skeletal tissue, these results suggest that a shift in the differentiation of mesenchymal cells from adipogenesis toward osteogenesis is a component of the OA pathophysiologic processes occurring in the tibial plateau joints of STR\/Ort 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