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 2

The Postn reporter activity labeled long-time (more than 6 months) retaining periosteal stem cells.

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The Postn reporter activity labeled long-time (more than 6 months) retai...
(A) The Postn reporter activity was shown in femur of Postn-CreERT2; tdTomato mice with tamoxifen injected for consecutive 3 days (n = 4). The graph shows the quantitative statistics of the ratio of tdTomato in cambium and periosteum. (B) Immunofluorescence staining of select MSCs markers and Ki67 in the metaphyseal femur of Postn-CreERT2; tdTomato mice (n = 3). The arrow indicates the colocalization, and the asterisk indicates the single staining of target protein. (C) The graph was the quantitative percentage of tdTomato+ cells that were immunofluorescence positive. (D) Flow cytometry analysis of select MSCs markers in tdTomato+ periosteal cells (n = 3) (tamoxifen injected for consecutive 3 days and sample acquired on fourth day). Pie chart illustrates the percentage of BCSP, Pre-BCSP, and SSC in tdTomato+ cells. (E) Immunofluorescence staining of POSTN and CTSK in femur of Postn-CreERT2; tdTomato mice 6 months after tamoxifen injection (n = 3). The arrowheads indicate the tdTomato signal in cortical bone, the diamonds indicate the tdTomato signal in endosteum, the arrows indicate the colocalization, and the asterisks indicate the single staining of target protein. (F) The left graph indicated the ratio of tdTomato+ cells in cambium layer and cortical bone osteocytes. The right graph indicated the percentage of tdTomato+ cells that were CTSK+ or POSTN+. (G) Ratio of tdTomato+ cells among cortical bone osteocytes after tracing for 0, 2, and 6 months (n = 4 for each group). Data were obtained from 3 independent experiments. Data are presented as mean ± SD. Red scale bar: 200 μm. Blue scale bar: 500 μm. White scale bar: 20 μm. F, fibrous layer; C, cambium layer; B, cortical bone.