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Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis

Author

Listed:
  • Bingyang Dai

    (The Chinese University of Hong Kong)

  • Jiankun Xu

    (The Chinese University of Hong Kong)

  • Xu Li

    (The Chinese University of Hong Kong)

  • Le Huang

    (The Chinese University of Hong Kong)

  • Chelsea Hopkins

    (The Chinese University of Hong Kong)

  • Honglian Wang

    (Affiliated Traditional Medicine Hospital of Southwest Medical University)

  • Hao Yao

    (The Chinese University of Hong Kong)

  • Jie Mi

    (The Chinese University of Hong Kong)

  • Lizhen Zheng

    (The Chinese University of Hong Kong)

  • Jiali Wang

    (Sun Yat-sen University)

  • Wenxue Tong

    (The Chinese University of Hong Kong)

  • Dick Ho-kiu Chow

    (The Chinese University of Hong Kong)

  • Ye Li

    (The Chinese University of Hong Kong)

  • Xuan He

    (The Chinese University of Hong Kong)

  • Peijie Hu

    (The Hong Kong Polytechnic University, Hung Hom)

  • Ziyi Chen

    (The Chinese University of Hong Kong)

  • Haiyue Zu

    (The Chinese University of Hong Kong)

  • Yixuan Li

    (The Affiliated Hospital of Nanjing University Medical School)

  • Yao Yao

    (The Affiliated Hospital of Nanjing University Medical School)

  • Qing Jiang

    (The Affiliated Hospital of Nanjing University Medical School)

  • Ling Qin

    (The Chinese University of Hong Kong)

Abstract

Epididymal white adipose tissue (eWAT) secretes an array of cytokines to regulate the metabolism of organs and tissues in high-fat diet (HFD)-induced obesity, but its effects on bone metabolism are not well understood. Here, we report that macrophages in eWAT are a main source of osteopontin, which selectively circulates to the bone marrow and promotes the degradation of the bone matrix by activating osteoclasts, as well as modulating bone marrow-derived macrophages (BMDMs) to engulf the lipid droplets released from adipocytes in the bone marrow of mice. However, the lactate accumulation induced by osteopontin regulation blocks both lipolysis and osteoclastogenesis in BMDMs by limiting the energy regeneration by ATP6V0d2 in lysosomes. Both surgical removal of eWAT and local injection of either clodronate liposomes (for depleting macrophages) or osteopontin-neutralizing antibody show comparable amelioration of HFD-induced bone loss in mice. These results provide an avenue for developing therapeutic strategies to mitigate obesity-related bone disorders.

Suggested Citation

  • Bingyang Dai & Jiankun Xu & Xu Li & Le Huang & Chelsea Hopkins & Honglian Wang & Hao Yao & Jie Mi & Lizhen Zheng & Jiali Wang & Wenxue Tong & Dick Ho-kiu Chow & Ye Li & Xuan He & Peijie Hu & Ziyi Chen, 2022. "Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27683-w
    DOI: 10.1038/s41467-021-27683-w
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    Cited by:

    1. Tammy Liu & Gerd Melkus & Tim Ramsay & Adnan Sheikh & Odette Laneuville & Guy Trudel, 2023. "Bone marrow adiposity modulation after long duration spaceflight in astronauts," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Yonggang Fan & Weixin Zhang & Xiusheng Huang & Mingzhe Fan & Chenhao Shi & Lantian Zhao & Guofu Pi & Huafeng Zhang & Shuangfei Ni, 2024. "Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Tongling Huang & Zhaocheng Lu & Zihui Wang & Lixin Cheng & Lu Gao & Jun Gao & Ning Zhang & Chang-An Geng & Xiaoli Zhao & Huaiyu Wang & Chi-Wai Wong & Kelvin W. K. Yeung & Haobo Pan & William Weijia Lu, 2024. "Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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