Peroxisome Proliferator-Activated Receptor α Facilitates Osteogenic Differentiation in MC3T3-E1 Cells via the Sirtuin 1-Dependent Signaling Pathway

Kai Gong; Bo Qu; Cairu Wang; Jingsong Zhou; Dongfa Liao; Wei Zheng; Xianming Pan

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자료유형: 학술저널

저자정보: Kai Gong (Chengdu Military General Hospital) Bo Qu (Chengdu Military General Hospital) Cairu Wang (Chengdu Military General Hospital) Jingsong Zhou (Chengdu Military General Hospital) Dongfa Liao (Chengdu Military General Hospital) Wei Zheng (Chengdu Military General Hospital) Xianming Pan (Chengdu Military General Hospital)

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제40권 제6호

발행연도: 2017.6

수록면: 393 - 400 (8page)

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by 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) γ. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPAR /δ-dependent manner. The ligand-activated transcription factor, PPAR , is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of PPAR in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to de-termine 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 PPAR , Sirt1 and osteogenic differentiation, but these effects were markedly reversed by PPAR overexpression. Moreover, siSirt1 attenuated the positive effects of PPAR on osteogenic differentiation, suggesting that PPAR promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between PPAR and Sirt1. These findings indicate that PPAR promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.

#diabetic osteoporosis #MC3T3-E1 #Sirt 1 #osteogenic differentiation #PPAR

참고문헌 (30)

참고문헌 신청

Ali, A. A. / 2005 / Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation / Endocrinology 146:1226~1235

Backesjo, C. M. / 2006 / Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells / J. Bone Miner Res 21:993~1002

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