{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T11:15:43Z","timestamp":1776942943811,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"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":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell\u2010to\u2010cell and cell\u2010to\u2010matrix interactions. GSL expression is decreased in the articular cartilage of humans with osteoarthritis (OA). This study was undertaken to determine the functional role of GSLs in cartilage metabolism related to OA pathogenesis in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated mice with knockout of the chondrocyte\u2010specific<jats:italic>Ugcg<\/jats:italic>gene, which encodes an initial enzyme of major GSL synthesis, using the Cre\/loxP system (Col2\u2010<jats:italic>Ugcg<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice). In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of GSLs on the cartilage degradation process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although Col2\u2010<jats:italic>Ugcg<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice developed and grew normally, OA changes in these mice were dramatically enhanced with aging, through the overexpression of matrix metalloproteinase 13 and chondrocyte apoptosis, compared to their wild\u2010type (WT) littermates. Col2\u2010<jats:italic>Ugcg<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice showed more severe instability\u2010induced pathologic OA in vivo and interleukin\u20101\u03b1 (IL\u20101\u03b1)\u2013induced cartilage degradation in vitro. IL\u20101\u03b1 stimulation of chondrocytes from WT mice significantly increased<jats:italic>Ugcg<\/jats:italic>messenger RNA expression and up\u2010regulated GSL metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that GSL deficiency in mouse chondrocytes enhances the development of OA. However, this deficiency does not affect the development and organization of cartilage tissue in mice at a young age. These findings indicate that GSLs maintain cartilage molecular metabolism and prevent disease progression, although GSLs are not essential for chondrogenesis of progenitor and stem cells and cartilage development in young mice. GSL metabolism in the cartilage is a potential target for developing a novel treatment for OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34463","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T01:28:01Z","timestamp":1330997281000},"page":"2579-2588","source":"Crossref","is-referenced-by-count":36,"title":["Interruption of glycosphingolipid synthesis enhances osteoarthritis development in 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