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

Leilei Zhong, Jiawei Lu, Jiankang Fang, Lutian Yao, Wei Yu, Tao Gui, Michael Duffy, Nicholas Holdreith, Catherine Bautista, Xiaobin Huang, Shovik Bandyopadhyay, Kai Tan, Chider Chen, Yongwon Choi, Jean X. Jiang, Shuying Yang, Wei Tong, Nathaniel Dyment, Ling Qin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere82112
JournaleLife
Volume12
DOIs
StatePublished - Feb 2023

Keywords

  • Bone
  • Csf1
  • Hematopoiesis
  • Marrow adipogenic lineage precursors
  • Osteoclasts

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience

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