Identification of Postn+ periosteal progenitor cells with bone regenerative potential
Bei Yin, Fangyuan Shen, Qingge Ma, Yongcheng Liu, Xianglong Han, Xuyu Cai, Yu Shi, Ling Ye
Bei Yin, Fangyuan Shen, Qingge Ma, Yongcheng Liu, Xianglong Han, Xuyu Cai, Yu Shi, Ling Ye
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Research Article Bone biology

Identification of Postn+ periosteal progenitor cells with bone regenerative potential

Abstract

Bone contains multiple pools of skeletal stem/progenitor cells (SSPCs), and SSPCs in periosteal compartments are known to exhibit higher regenerative potential than those in BM and endosteal compartments. However, the in vivo identity and hierarchical relationships of periosteal SSPCs (P-SSPCs) remain unclear due to a lack of reliable markers to distinguish BM SSPCs and P-SSPCs. Here, we found that periosteal mesenchymal progenitor cells (P-MPs) in periosteum can be identified based on Postn-CreERT2 expression. Postn-expressing periosteal subpopulation produces osteolineage descendants that fuel bones to maintain homeostasis and support regeneration. Notably, Postn+ P-MPs are likely derived from Gli1+ skeletal stem cells (SSCs). Ablation of Postn+ cells results in impairments in homeostatic cortical bone architecture and defects in fracture repair. Genetic deletion of Igf1r in Postn+ cells dampens bone fracture healing. In summary, our study provides a mechanistic understanding of bone regeneration through the regulation of region-specific Postn+ P-MPs.

Authors

Bei Yin, Fangyuan Shen, Qingge Ma, Yongcheng Liu, Xianglong Han, Xuyu Cai, Yu Shi, Ling Ye

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Figure 3

Postn reporter activity marked periosteal cells that contributed to bone healing.

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Postn reporter activity marked periosteal cells that contributed to bon...
(A) Distribution of Postn reporter activity and Ki67 immunofluorescence staining in day 10 callus of Postn-CreERT2; tdTomato mice with tamoxifen injection at postfracture days 8 and 9 (n = 3). (B and C) Ratio of dTomato+ cells in hard and soft callus and immunofluorescence staining of OSX, ACAN, POSTN, and CTSK in day 10 callus with tamoxifen injection 8 days before bone fracture for consecutive 3 days (n = 4). The graph indicates percentage of tdTomato+ cells. (D) Distribution of tdTomato signal and immunofluorescence staining of POSTN and CTSK 2 months after fracture with tamoxifen injection 8 days before the bone fracture (n = 5). The graph indicated the ratio of tdTomato+ cells in cambium, cortical bone, endosteum, trabecular bone, POSTN-expressing cells, and CTSK-expressing cells. (E and F) Ratio of tdTomato+ cells in hard and soft callus and immunofluorescence staining of OSX, ACAN, POSTN, and CTSK in day 10 callus with tamoxifen injection for 3 days starting from the fracture day (n = 4). The graph indicated percentage of tdTomato+ cells. (G) Distribution of tdTomato+ cells and immunofluorescence staining of POSTN and CTSK 2 months after fracture with tamoxifen injection starting at the fracture day for 3 days (n = 3). The graph indicates the ratio of tdTomato+ cells in cambium, cortical bone, endosteum, trabecular bone, POSTN-expressing, and CTSK-expressing cells. Data were obtained from 3 independent experiments. Data are presented as mean ± SD. Blue scale bar: 500 μm. Red scale bar: 200 μm. The arrow indicates the colocalization. White scale bar: 20 μm. Orange scale bar: 5 μm. F, fibrous layer; C, cambium layer; B, cortical bone; E, endosteum; P, periosteum.