Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis and bone mass

  1. Kazuki Inoue
  2. Yongli Qin
  3. Yuhan Xia
  4. Jie Han
  5. Ruoxi Yuan
  6. Jun Sun
  7. Ren Xu
  8. Jean X Jiang
  9. Matthew B Greenblatt
  10. Baohong Zhao  Is a corresponding author
  1. Hospital for Special Surgery, United States
  2. First Affiliated Hospital of Xiamen University, China
  3. Weill Cornell, United States
  4. The University of Texas Health Science Center at San Antonio, United States

Abstract

M-CSF is a critical growth factor for myeloid lineage cells, including monocytes, macrophages and osteoclasts. Tissue-resident macrophages in most organs rely on local M-CSF. However, it is unclear what specific cells in the bone marrow produce M-CSF to maintain myeloid homeostasis. Here, we found that Adipoq-lineage progenitors but not mature adipocytes in bone marrow or in peripheral adipose tissue, are a major cellular source of M-CSF, with these Adipoq-lineage progenitors producing M-CSF at levels much higher than those produced by osteoblast lineage cells. Deficiency of M-CSF in bone marrow Adipoq-lineage progenitors drastically reduces the generation of bone marrow macrophages and osteoclasts, leading to severe osteopetrosis in mice. Furthermore, the osteoporosis in ovariectomized mice can be significantly alleviated by the absence of M-CSF in bone marrow Adipoq-lineage progenitors. Our findings identify bone marrow Adipoq-lineage progenitors as a major cellular source of M-CSF in bone marrow and reveal their crucial contribution to bone marrow macrophage development, osteoclastogenesis, bone homeostasis and pathological bone loss.

Data availability

The current manuscript does not contain sequencing data.The Source Data files for figures have been submitted.

The following previously published data sets were used

Article and author information

Author details

  1. Kazuki Inoue

    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6305-9374
  2. Yongli Qin

    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, United States
    Competing interests
    No competing interests declared.
  3. Yuhan Xia

    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, United States
    Competing interests
    No competing interests declared.
  4. Jie Han

    ICMRS Collaborating Center for Skeletal Stem Cells, First Affiliated Hospital of Xiamen University, Xiamen, China
    Competing interests
    No competing interests declared.
  5. Ruoxi Yuan

    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, United States
    Competing interests
    No competing interests declared.
  6. Jun Sun

    Pathology and Laboratory Medicine, Weill Cornell, New York, United States
    Competing interests
    No competing interests declared.
  7. Ren Xu

    ICMRS Collaborating Center for Skeletal Stem Cells, First Affiliated Hospital of Xiamen University, Xiamen, China
    Competing interests
    No competing interests declared.
  8. Jean X Jiang

    Department of Biochemistry and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, United States
    Competing interests
    Jean X Jiang, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2185-5716
  9. Matthew B Greenblatt

    Department of Pathology and Laboratory Medicine, Weill Cornell, New York, United States
    Competing interests
    No competing interests declared.
  10. Baohong Zhao

    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, United States
    For correspondence
    zhaob@hss.edu
    Competing interests
    Baohong Zhao, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1286-0919

Funding

National Institutes of Health (AR078212,AR068970,AR071463)

  • Baohong Zhao

National Institutes of Health (AR075585)

  • Matthew B Greenblatt

National Institutes of Health (AG045040)

  • Jean X Jiang

Tow Foundation (Rosensweig Genomics Center at the Hospital for Special Surgery)

  • Baohong Zhao

Welch Foundation (AQ-1507)

  • Jean X Jiang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mei Wan, Johns Hopkins University, United States

Ethics

Animal experimentation: All mouse experiments were approved by Institutional Animal Care and Use Committee of the Hospital for Special Surgery and Weill Cornell Medical College (protocol numbers: 2016-0001 and 0004).

Version history

  1. Received: July 23, 2022
  2. Preprint posted: July 30, 2022 (view preprint)
  3. Accepted: February 12, 2023
  4. Accepted Manuscript published: February 13, 2023 (version 1)
  5. Version of Record published: March 10, 2023 (version 2)

Copyright

© 2023, Inoue et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kazuki Inoue
  2. Yongli Qin
  3. Yuhan Xia
  4. Jie Han
  5. Ruoxi Yuan
  6. Jun Sun
  7. Ren Xu
  8. Jean X Jiang
  9. Matthew B Greenblatt
  10. Baohong Zhao
(2023)
Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis and bone mass
eLife 12:e82118.
https://doi.org/10.7554/eLife.82118

Share this article

https://doi.org/10.7554/eLife.82118

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