SIRT1 suppresses high glucose and palmitate-induced osteoclast differentiation via deacetylating p66Shc.
Authors of this article are:
Qu B, Gong K, Yang H, Li Y, Jiang T, Zeng Z, Cao Z, Pan X.
A summary of the article is shown below:
Findings concerning the role of diabetes mellitus (DM) in osteoclast differentiation are contradictory in vivo and in vitro. Sirtuin 1 (SIRT1) can inhibit RANKL-induced osteoclastogenesis and deacetylate p66Shc suppress its phosphorylation in high glucose (HG)-stimulated human umbilical vein endothelial cells. This study aimed to investigate the role and mechanism of SIRT1 in DM-related osteoclast differentiation. Osteoclast precursors were cultured with HG and palmitate (PA), with or without resveratrol/sirtinol. TRAP staining was used to evaluate osteoclast formation. The expression of SIRT1, RANK, RANKL, OPG, NFATc1, TRAP, c-fos, p66Shc, phospho-p66Shc (S36), phospho-NF-κBp65 (p-p65), and IκB was determined by real-time PCR or western blotting. Lysine acetylation of p66Shc was assayed by immunoprecipitation. Reactive oxygen species (ROS) production was analyzed by DCFH-DA fluorescence. p66Shc siRNA and PDTC were used to confirm the mechanism of SIRT1 in osteoclastogenesis. We found HG and PA enhanced osteoclast differentiation, decreased SIRT1 and OPG expression, and increased levels of RANK, RANKL, NFATc1, TRAP, and c-fos. Upregulation of SIRT1 by resveratrol inhibited HG- and PA-induced osteoclast differentiation, whereas sirtinol further enhanced it. Resveratrol suppressed lysine acetylation and S36 phosphorylation of p66Shc, ROS production, and NF-κB activation induced by HG and PA, while sirtinol boosted these processes. p66Shc siRNA abrogated HG- and PA-induced ROS production and NF-κB activation. In addition, p66Shc siRNA and PDTC greatly suppressed the expression of RANK and RANKL induced by HG and PA. In conclusion, this study confirms the role of DM in osteoclast differentiation in vitro. SIRT1 suppresses HG- and PA-induced osteoclast differentiation via p66Shc/ROS/NF-κB signaling.
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This article is a good source of information and a good way to become familiar with topics such as:
Diabetes mellitus;NF-κB;Osteoclast differentiation;ROS;SIRT1;p66Shc
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