{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:35:33Z","timestamp":1788867333804,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T00:00:00Z","timestamp":1444262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CBET\u20100966920"],"award-info":[{"award-number":["CBET\u20100966920"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Osteoarthritis (OA) is a widespread chronic joint disease characterized by articular cartilage destruction and accompanied by pain and disability. In this study, we found that the expression of Insulin\u2010like Growth Factor II (IGF\u2010II) was reduced in articular cartilage in human OA patients as well as in the murine experimental OA model of destabilization of the medial meniscus (DMM). In primary human articular chondrocytes, ectopic expression of lentiviral IGF\u2010II inhibited pro\u2010inflammatory cytokine IL\u20101\u03b2\u2010induced NF\u2010\u03baB activation as well as catabolic gene expression. Interestingly, IGF\u2010II did not significantly alter the phosphorylation states of ERK1\/2 or Akt, which are kinases typically activated by IGF\u2010I. Instead, it induced the activity of phospholipase C (PLC) and a PLC inhibitor blocked the inhibitory activity of IGF\u2010II against IL\u20101\u03b2, suggesting that this activity is mediated through PLC. Furthermore, IGF\u2010II increased cartilage matrix levels and decreased MMP13 protein expression in explanted human OA cartilage cultures in vitro. In the in vivo DMM model, intraarticular injection of lentiviral IGF\u2010II led to enhanced cartilage matrix levels and decreased MMP13 protein expression, as well as reduced osteophyte formation and subchondral bone sclerosis. Therefore, our results suggest that IGF\u2010II can promote cartilage integrity and halt knee joint destruction in OA. J. Cell. Biochem. 116: 2858\u20132869, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25232","type":"journal-article","created":{"date-parts":[[2015,5,26]],"date-time":"2015-05-26T23:15:25Z","timestamp":1432682125000},"page":"2858-2869","source":"Crossref","is-referenced-by-count":29,"title":["\u00ad\u00ad\u00ad\u00ad\u00adInsulin\u2010Like Growth Factor II (IGF\u2010II) Inhibits IL\u20101\u03b2\u2010Induced Cartilage Matrix Loss and Promotes Cartilage Integrity in Experimental Osteoarthritis"],"prefix":"10.1002","volume":"116","author":[{"given":"Tomoya","family":"Uchimura","sequence":"first","affiliation":[{"name":"Program in Cellular, Molecular and Developmental Biology Sackler School of Graduate Biomedical Sciences Tufts University School of Medicine 136 Harrison Avenue Boston Massachusetts 02111"},{"name":"Department of Integrative Physiology and Pathobiology Tufts University School of Medicine 136 Harrison Avenue Boston Massachusetts 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