Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration

Bo Gao, Ruoxian Deng, Yu Chai, Hao Chen, Bo Hu, Xiao Wang, Shouan Zhu, Yong Cao, Shuangfei Ni, Mei Wan, Liu Yang, Zhuojing Luo, Xu Cao

Research output: Contribution to journalArticle

Abstract

Cortical bones account for more than 80% of human bone mass. The periosteum, a thin tissue that covers almost the entire bone surface, is essential for bone formation and regeneration. However, its osteogenic and bone regenerative abilities are not well studied. In this study, we found that macrophage-lineage cells recruit periosteum-derived cells (PDCs) for cortical bone formation. Knockout of colony-stimulating factor-1 eliminated macrophage-lineage cells and resulted in loss of PDCs with impaired periosteal bone formation. Moreover, macrophage-lineage tartrate-resistant acid phosphatase–positive (TRAP+) cells induced transcriptional expression of periostin and recruitment of PDCs to the periosteal surface through secretion of PDGF-BB, where the recruited PDCs underwent osteoblast differentiation coupled with type H vessel formation. We also found that subsets of Nestin+ and LepR+CD45–Ter119–CD31– cells (LepR+ PDCs) possess multipotent and self-renewal abilities and contribute to cortical bone formation. Nestin+ PDCs are found primarily during bone development, whereas LepR+ PDCs are essential for bone homeostasis in adult mice. Importantly, conditional knockout of Pdgfr-β in LepR+ cells impaired periosteal bone formation and regeneration. These findings uncover the essential role of periosteal macrophage-lineage cells in regulating periosteum homeostasis and regeneration.

Original languageEnglish (US)
Pages (from-to)2578-2594
Number of pages17
JournalJournal of Clinical Investigation
Volume129
Issue number6
DOIs
StatePublished - Jun 3 2019

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Periosteum
Osteogenesis
Regeneration
Macrophages
Bone and Bones
Nestin
Bone Regeneration
Homeostasis
Macrophage Colony-Stimulating Factor
Bone Development
Osteoblasts

ASJC Scopus subject areas

  • Medicine(all)

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Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration. / Gao, Bo; Deng, Ruoxian; Chai, Yu; Chen, Hao; Hu, Bo; Wang, Xiao; Zhu, Shouan; Cao, Yong; Ni, Shuangfei; Wan, Mei; Yang, Liu; Luo, Zhuojing; Cao, Xu.

In: Journal of Clinical Investigation, Vol. 129, No. 6, 03.06.2019, p. 2578-2594.

Research output: Contribution to journalArticle

Gao, Bo ; Deng, Ruoxian ; Chai, Yu ; Chen, Hao ; Hu, Bo ; Wang, Xiao ; Zhu, Shouan ; Cao, Yong ; Ni, Shuangfei ; Wan, Mei ; Yang, Liu ; Luo, Zhuojing ; Cao, Xu. / Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration. In: Journal of Clinical Investigation. 2019 ; Vol. 129, No. 6. pp. 2578-2594.
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AU - Deng, Ruoxian

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AU - Chen, Hao

AU - Hu, Bo

AU - Wang, Xiao

AU - Zhu, Shouan

AU - Cao, Yong

AU - Ni, Shuangfei

AU - Wan, Mei

AU - Yang, Liu

AU - Luo, Zhuojing

AU - Cao, Xu

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