Identification of Postn+ periosteal progenitor cells with bone regenerative potential

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) rema...

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Bibliographic Details
Published in:JCI insight 2024-10, Vol.9 (19)
Main Authors: Yin, Bei, Shen, Fangyuan, Ma, Qingge, Liu, Yongcheng, Han, Xianglong, Cai, Xuyu, Shi, Yu, Ye, Ling
Format: Article
Language:English
Subjects:
Animals
Bone Regeneration
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Differentiation
Female
Fracture Healing
Male
Mesenchymal Stem Cells - metabolism
Mice
Osteogenesis - genetics
Osteogenesis - physiology
Periosteum - cytology
Periosteum - metabolism
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Summary: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.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.182524