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• W2108014352 abstract "<h3>Objectives</h3> Important roles for SIRT1 are implicated in ageing and age-related diseases. The role of SIRT1 in osteoarthritis (OA), however, remains partially unknown. To investigate the role of SIRT1 in chondrocytes in vivo, cartilage-specific <i>Sirt1-</i>conditional knockout (CKO) mice were analysed using an experimental OA model. <h3>Methods</h3> OA was surgically induced in 8-week-old C57BL6/J (wild-type) mice and <i>Sirt1</i>-CKO (<i>Sirt1</i>^flox/^flox; <i>Col2a1-Cre</i>) mice generated using the Cre-<i>lox</i>P system. We examined changes in Sirt1 protein during the development of surgically-induced OA and during ageing in wild-type mice. OA progression in <i>Sirt1</i>-CKO mice was evaluated histologically at 2, 4 and 8 weeks after surgery, and at 1 year of age without surgery compared with control (<i>Sirt1</i>^flox/^flox) mice. <h3>Results</h3> The number of Sirt1-positive chondrocytes decreased during ageing, and although it was increased at 2 weeks after surgery, then gradually decreased to the presurgical level during the progression of OA in wild-type mice. <i>Sirt1</i>-CKO mice showed no obvious skeletal abnormalities. The histological OA score was significantly higher in 1-year-old <i>Sirt1</i>-CKO mice than in control mice. <i>Sirt1</i>-CKO mice showed accelerated OA progression at 2 and 4 (but not 8) weeks compared with control mice. Immunohistochemical analysis revealed increases in type X collagen, matrix metalloproteinase 13, a disintegrin and metalloproteinase with thrombospondin motifs-5, apoptotic markers, and acetylated nuclear factor-κB p65 in <i>Sirt1</i>-CKO mice compared with control mice 2 weeks after surgery. <h3>Conclusions</h3> Loss of Sirt1 in chondrocytes led to the accelerated development of OA in mice. Our observations suggest that SIRT1 has a preventive role against the development of OA." @default.
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• W2108014352 date "2013-05-30" @default.
• W2108014352 modified "2023-10-02" @default.
• W2108014352 title "Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice" @default.
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• W2108014352 doi "https://doi.org/10.1136/annrheumdis-2012-202620" @default.
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