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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

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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 7

The deletion of Postn+ cells impaired bone healing.

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The deletion of Postn+ cells impaired bone healing.
(A) Distribution of ...
(A) Distribution of tdTomato+ cells in day 7 callus of Postn-CreERT2; tdTomato (CON) and Postn-CreERT2; tdTomato; DTA (DTA) mice with 5 day tamoxifen administration starting from the fracture day. B, cortical bone; Ca, callus (n = 3 per genotype). (B–D) The H&E staining (B), safranin O (C), and Masson’s trichrome staining (D) of day 14 callus in DTA mice and control mice (n = 3 per genotype). The graph illustrates the percentage of cartilage area (C) and bone area (D). (E) The immunofluorescence staining of OSX (Sp7) in day 14 callus in the Postn-CreERT2; tdTomato; DTA mice and control mice (n = 3 per genotype). The graph illustrates the ratio of tdTomato+ in OSX-expressing cells. (F and G) The μCT reconstructions (F) and comparative parameters (G) of the callus 1 month post fracture (n = 4 in CON group and n = 3 in DTA group). The analysis included the bone volume (B.V), bone volume/tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and bone mineral density (BMD). (H) The Masson’s trichrome staining of the fractured bone in DTA and control mice 1 month after fracture (n = 4 in CON group and n = 3 in DTA group). Data were obtained from 3 independent experiments. Standard 2-tailed Student’s t test. Data are presented as mean ± SD. Red scale bar: 1 mm. Black scale bar: 500 μm. Blue scale bar: 50 μm.

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