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Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis

Author

Listed:
  • Yuqi Guo

    (New York University College of Dentistry)

  • Chengzhi Xie

    (New York University College of Dentistry
    Present address: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina 27710, USA)

  • Xiyan Li

    (Stanford University)

  • Jian Yang

    (New York University College of Dentistry)

  • Tao Yu

    (New York University College of Dentistry
    Institute for Genomic Engineered Animal Models of Human Diseases)

  • Ruohan Zhang

    (New York University College of Dentistry)

  • Tianqing Zhang

    (New York University College of Dentistry)

  • Deepak Saxena

    (New York University College of Dentistry)

  • Michael Snyder

    (Stanford University)

  • Yingjie Wu

    (Institute for Genomic Engineered Animal Models of Human Diseases
    Advanced Institute for Medical Science, Dalian Medical University)

  • Xin Li

    (New York University College of Dentistry
    New York University Langone Medical Center
    Perlmutter Cancer Institute, New York University Langone Medical Center)

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.

Suggested Citation

  • Yuqi Guo & Chengzhi Xie & Xiyan Li & Jian Yang & Tao Yu & Ruohan Zhang & Tianqing Zhang & Deepak Saxena & Michael Snyder & Yingjie Wu & Xin Li, 2017. "Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15621
    DOI: 10.1038/ncomms15621
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