Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis

Yuqi Guo, Chengzhi Xie, Xiyan Li, Jian Yang, Tao Yu, Ruohan Zhang, Tianqing Zhang, Deepak Saxena, Michael Snyder, Yingjie Wu, Xin Li

Research output: Contribution to journalArticle

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 normoglycaemic mice. One hundred and forty-Two metabolites are substantially regulated in BMSCs from T2D mice, with the tricarboxylic acid (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 BMSCs 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 targeting the receptor activation inhibit osteoclastogenesis. This study reveals a metabolite-mediated mechanism of osteoclastogenesis modulation that contributes to bone dysregulation in metabolic disorders.

Original languageEnglish (US)
Article number15621
JournalNature Communications
Volume8
DOIs
StatePublished - May 31 2017

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diabetes mellitus
Succinic Acid
G-Protein-Coupled Receptors
Mesenchymal Stromal Cells
Osteogenesis
Type 2 Diabetes Mellitus
bone marrow
metabolites
Medical problems
Bone
hyperglycemia
Citric Acid Cycle
proteins
mice
Hyperglycemia
Metabolites
bones
Bone and Bones
Metabolomics
disorders

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis. / Guo, Yuqi; Xie, Chengzhi; Li, Xiyan; Yang, Jian; Yu, Tao; Zhang, Ruohan; Zhang, Tianqing; Saxena, Deepak; Snyder, Michael; Wu, Yingjie; Li, Xin.

In: Nature Communications, Vol. 8, 15621, 31.05.2017.

Research output: Contribution to journalArticle

Guo, Y, Xie, C, Li, X, Yang, J, Yu, T, Zhang, R, Zhang, T, Saxena, D, Snyder, M, Wu, Y & Li, X 2017, 'Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis', Nature Communications, vol. 8, 15621. https://doi.org/10.1038/ncomms15621
Guo, Yuqi ; Xie, Chengzhi ; Li, Xiyan ; Yang, Jian ; Yu, Tao ; Zhang, Ruohan ; Zhang, Tianqing ; Saxena, Deepak ; Snyder, Michael ; Wu, Yingjie ; Li, Xin. / Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis. In: Nature Communications. 2017 ; Vol. 8.
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AU - Zhang, Tianqing

AU - Saxena, Deepak

AU - Snyder, Michael

AU - Wu, Yingjie

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