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Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox

Author

Listed:
  • Zhen-Xing Wang

    (Central South University
    Central South University)

  • Zhong-Wei Luo

    (Central South University
    Central South University)

  • Fu-Xing-Zi Li

    (Central South University)

  • Jia Cao

    (Central South University
    Central South University)

  • Shan-Shan Rao

    (Central South University
    Central South University)

  • Yi-Wei Liu

    (Central South University
    Central South University)

  • Yi-Yi Wang

    (Central South University
    Central South University)

  • Guo-Qiang Zhu

    (Central South University
    Central South University)

  • Jiang-Shan Gong

    (Central South University
    Central South University)

  • Jing-Tao Zou

    (Central South University
    Central South University)

  • Qiang Wang

    (Zhejiang University School of Medicine, Hangzhou)

  • Yi-Juan Tan

    (Central South University
    Central South University)

  • Yan Zhang

    (Central South University)

  • Yin Hu

    (Central South University)

  • You-You Li

    (Central South University
    Central South University)

  • Hao Yin

    (Central South University
    Central South University)

  • Xiao-Kai Wang

    (Central South University)

  • Ze-Hui He

    (Central South University
    Central South University)

  • Lu Ren

    (Central South University)

  • Zheng-Zhao Liu

    (Central South University
    Central South University
    Central South University
    Aging and Regenerative Medicine)

  • Xiong-Ke Hu

    (Central South University)

  • Ling-Qing Yuan

    (Central South University)

  • Ran Xu

    (Central South University)

  • Chun-Yuan Chen

    (Central South University
    Central South University)

  • Hui Xie

    (Central South University
    Central South University
    Central South University
    Central South University)

Abstract

Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.

Suggested Citation

  • Zhen-Xing Wang & Zhong-Wei Luo & Fu-Xing-Zi Li & Jia Cao & Shan-Shan Rao & Yi-Wei Liu & Yi-Yi Wang & Guo-Qiang Zhu & Jiang-Shan Gong & Jing-Tao Zou & Qiang Wang & Yi-Juan Tan & Yan Zhang & Yin Hu & Yo, 2022. "Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29191-x
    DOI: 10.1038/s41467-022-29191-x
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    References listed on IDEAS

    as
    1. Yuqin Men & Julia Yelick & Shijie Jin & Yang Tian & Ming Sum R. Chiang & Haruki Higashimori & Eoin Brown & Rachel Jarvis & Yongjie Yang, 2019. "Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    2. Duk-Hwa Kwon & Gwang Hyeon Eom & Jeong Hyeon Ko & Sera Shin & Hosouk Joung & Nakwon Choe & Yoon Seok Nam & Hyun-Ki Min & Taewon Kook & Somy Yoon & Wanseok Kang & Yong Sook Kim & Hyung Seok Kim & Hyuck, 2016. "MDM2 E3 ligase-mediated ubiquitination and degradation of HDAC1 in vascular calcification," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    3. Yalin Zhang & Min Soo Kim & Baosen Jia & Jingqi Yan & Juan Pablo Zuniga-Hertz & Cheng Han & Dongsheng Cai, 2017. "Hypothalamic stem cells control ageing speed partly through exosomal miRNAs," Nature, Nature, vol. 548(7665), pages 52-57, August.
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