Mol. Cells 2017; 40(6): 393~400
Peroxisome Proliferator-Activated Receptor alpha Facilitates Osteogenic Differentiation in MC3T3-E1 Cells via the Sirtuin 1-Dependent Signaling Pathway
Kai Gong1,2, Bo Qu1,2, Cairu Wang1, Jingsong Zhou1, Dongfa Liao1, Wei Zheng1, and Xianming Pan1,*
1Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu Road, Chengdu, Sichuan 610083, China,
2These authors contributed equally to this work.
Received February 6, 2017; Revised April 20, 2017; Accepted May 3, 2017.; Published online June 14, 2017.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disease characterized by a lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a NAD+-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) gamma. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPARbeta/δ- dependent manner. The ligand-activated transcription factor, PPARalpha, is another isotype of the peroxisome proliferatoractivated receptors family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of PPARalpha in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of PPARalpha and Sirt1 and osteogenic differentiation, but these effects were markedly reversed by PPARalpha overexpression. Moreover, siSirt1 attenuated the positive effects of PPARalpha on osteogenic differentiation, suggesting that PPARalpha promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between PPARalpha and Sirt1. These findings indicate that PPARalpha promotes osteogenic differentiation via the Sirt1- dependent signaling pathway.
Keywords: diabetic osteoporosis, MC3T3-E1, Sirt 1, osteogenic
differentiation, PPARalpha

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30 June 2017 Volume 40,
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