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Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis

Li, Xin and Xie, Chengzhi and Li, Xiyan and Yang, Jian and Yu, Tao and Zhang, Ruohan and Zhang, Tianqing and Saxena, Deepak and Snyder, Michael and Wu, Yingjie and Li, Xin (2017) Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis. Nature communications, 8. p. 15621. ISSN 2041-1723

Abstract

The mechanism underlying bone impairment in patients with diabetes mellitus, a
metabolic disorder characterized by chronic hyperglycaemia and dysregulation in metabolism, is
unclear. Here we show the difference in the metabolomics of bone marrow stromal cells
(BMSCs) derived from hyperglycaemic (type 2 diabetes mellitus, [T2D]) and normal glycemic
mice. 142 metabolites are substantially regulated in BMSC from T2D mice, with the TCA cycle
being one of the primary metabolic pathways impaired by hyperglycaemia. Importantly,
succinate, an intermediate metabolite in the TCA cycle, is increased by 24-fold in BMSC from
T2D mice. Succinate functions as an extracellular ligand through binding to its specific receptor
on osteoclastic lineage cells and stimulates osteoclastogenesis in vitro and in vivo. Strategies
blocking the receptor activation inhibit osteoclastogenesis. This study reveals a metabolitemediated
mechanism of osteoclastogenesis modulation that contributes to bone dysregulation in
metabolic disorders.

Item Type: Article
Date Deposited: 21 Jun 2017 00:45
Last Modified: 21 Jun 2017 00:45
URI: https://oak.novartis.com/id/eprint/32691

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