期刊
STEM CELL REPORTS
卷 15, 期 4, 页码 955-967出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2020.08.005
关键词
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资金
- Inserm ATIP-Avenir, France
- Osteosynthesis and Trauma Care Foundation, Switzerland
- Fondation de l'Avenir, France
- Agence Nationale de la Recherche, France [ANR-13-BSV1, ANR-18-CE14-0033]
- NIAMS, United States [R01 AR072707]
- Paris University
- Agence Nationale de la Recherche (ANR) [ANR-18-CE14-0033] Funding Source: Agence Nationale de la Recherche (ANR)
Most organs and tissues in the body, including bone, can repair after an injury due to the activation of endogenous adult stem/progenitor cells to replace the damaged tissue. Inherent dysfunctions of the endogenous stem/progenitor cells in skeletal repair disorders are still poorly understood. Here, we report that Fgfr3(Y637C/+) over-activating mutation in Prx1-derived skeletal stem/progenitor cells leads to failure of fracture consolidation. We show that periosteal cells (PCs) carrying the Fgfr3(Y637C/+) mutation can engage in osteogenic and chondrogenic lineages, but following transplantation do not undergo terminal chondrocyte hypertrophy and transformation into bone causing pseudarthrosis. Instead, Prx1(Cr)e;Fgfr3(Y637C/+) PCs give rise to fibrocartilage and fibrosis. Conversely, wild-type PCs transplanted at the fracture site of Prx1(Cre);Fgfr3(Y637C/+) mice allow hypertrophic cartilage transition to bone and permit fracture consolidation. The results thus highlight cartilage-to-bone transformation as a necessary step for bone repair and FGFR3 signaling within PCs as a key regulator of this transformation.
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