Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis and bone mass
- Hospital for Special Surgery, United States
- First Affiliated Hospital of Xiamen University, China
- Weill Cornell, United States
- 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.
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Connecting the Dots: Resolving the Bone Marrow Niche HeterogeneityBroad Institute Single Cell Portal SCP1248.
Article and author information
Author details
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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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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