1. Medicine

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

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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.

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).

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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Further reading

    1. Cell Biology
    2. Medicine

    Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone

    Leilei Zhong, Jiawei Lu ... Ling Qin
    Research Article Updated

    Colony-stimulating factor 1 (Csf1) is an essential growth factor for osteoclast progenitors and an important regulator for bone resorption. It remains elusive which mesenchymal cells synthesize Csf1 to stimulate osteoclastogenesis. We recently identified a novel mesenchymal cell population, marrow adipogenic lineage precursors (MALPs), in bone. Compared to other mesenchymal subpopulations, MALPs expressed Csf1 at a much higher level and this expression was further increased during aging. To investigate its role, we constructed MALP-deficient Csf1 CKO mice using AdipoqCre. These mice had increased femoral trabecular bone mass, but their cortical bone appeared normal. In comparison, depletion of Csf1 in the entire mesenchymal lineage using Prrx1Cre led to a more striking high bone mass phenotype, suggesting that additional mesenchymal subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts in the femoral secondary spongiosa region of Csf1 CKOAdipoq mice, but not at the chondral-osseous junction nor at the endosteal surface of cortical bone. Moreover, Csf1 CKOAdipoq mice were resistant to LPS-induced calvarial osteolysis. Bone marrow cellularity, hematopoietic progenitors, and macrophages were also reduced in these mice. Taken together, our studies demonstrate that MALPs synthesize Csf1 to control bone remodeling and hematopoiesis.