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Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration
Bo Gao, … , Zhuojing Luo, Xu Cao
Bo Gao, … , Zhuojing Luo, Xu Cao
Published April 4, 2019
Citation Information: J Clin Invest. 2019;129(6):2578-2594. https://doi.org/10.1172/JCI98857.
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Research Article Bone biology Article has an altmetric score of 6

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

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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.

Authors

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

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Figure 5

PDGF-BB secreted by TRAP+ cells recruits PDCs to the periosteal surface for cortical bone formation.

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PDGF-BB secreted by TRAP+ cells recruits PDCs to the periosteal surface ...
(A) Representative images of coronal tibia diaphyseal periosteum sections from Trap-cre Pdgfbfl/fl mice and Pdgfbfl/fl mice stained for TRAP and Nestin (top) and TRAP and LepR (bottom). (B and C) Quantification of Nestin+ cells (B) and LepR+ cells (C) in the inner layer of periosteum (no. cells/P.BS) and/or whole periosteum (no. cells/periosteum). Scale bars: 20 μm (n = 5 mice/group). (D and E) Percentage of Ki-67+ (D) or Brdu+ (E) cells in Nestin+ or LepR+ cells on periosteum (n = 5 mice/group). (F) Tibiae 14 days after cortical bone defect surgery. Representative μCT images of tibial cortex and quantification of the newly formed bone volume (BV/TV). Scale bars: 1 mm (n = 5 mice/group). (G) H&E staining of defect site sections. Red boxes indicate the defect sites. Scale bars: 200 μm (n = 5 mice/group). (H–J). Representative images of defect site sections stained for Nestin and LepR. Quantification of Nestin+ cells (I) and LepR+ cells (J) in the defect sites. Scale bars: 100 μm (n = 5 mice/group). Dashed lines indicate the limit between periosteum and cortical bone. Data are presented as mean ± SEM. *P < 0.05; **P < 0.01. C, cortical bone; P, periosteum; NS, not significant as determined by 2-tailed Student t test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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