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Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

Author

Listed:
  • Yuan Wang

    (Sichuan University)

  • Peng Deng

    (UCLA)

  • Yuting Liu

    (Sichuan University)

  • Yunshu Wu

    (Sichuan University)

  • Yaqian Chen

    (Sichuan University)

  • Yuchen Guo

    (Sichuan University)

  • Shiwen Zhang

    (Sichuan University)

  • Xiaofei Zheng

    (Sichuan University
    The First Affiliated Hospital of Zhengzhou University)

  • Liyan Zhou

    (Sichuan University)

  • Weiqing Liu

    (Sichuan University)

  • Qiwen Li

    (Sichuan University)

  • Weimin Lin

    (Sichuan University)

  • Xingying Qi

    (Sichuan University)

  • Guomin Ou

    (Sichuan University)

  • Cunyu Wang

    (UCLA)

  • Quan Yuan

    (Sichuan University)

Abstract

Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases.

Suggested Citation

  • Yuan Wang & Peng Deng & Yuting Liu & Yunshu Wu & Yaqian Chen & Yuchen Guo & Shiwen Zhang & Xiaofei Zheng & Liyan Zhou & Weiqing Liu & Qiwen Li & Weimin Lin & Xingying Qi & Guomin Ou & Cunyu Wang & Qua, 2020. "Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19360-1
    DOI: 10.1038/s41467-020-19360-1
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    Cited by:

    1. Caojie Liu & Qiuchan Xiong & Qiwen Li & Weimin Lin & Shuang Jiang & Danting Zhang & Yuan Wang & Xiaobo Duan & Ping Gong & Ning Kang, 2022. "CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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