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FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair.


ABSTRACT: 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 Fgfr3Y637C/+ over-activating mutation in Prx1-derived skeletal stem/progenitor cells leads to failure of fracture consolidation. We show that periosteal cells (PCs) carrying the Fgfr3Y637C/+ mutation can engage in osteogenic and chondrogenic lineages, but following transplantation do not undergo terminal chondrocyte hypertrophy and transformation into bone causing pseudarthrosis. Instead, Prx1Cre;Fgfr3Y637C/+ PCs give rise to fibrocartilage and fibrosis. Conversely, wild-type PCs transplanted at the fracture site of Prx1Cre;Fgfr3Y637C/+ 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.

SUBMITTER: Julien A 

PROVIDER: S-EPMC7561512 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair.

Julien Anais A   Perrin Simon S   Duchamp de Lageneste Oriane O   Carvalho Caroline C   Bensidhoum Morad M   Legeai-Mallet Laurence L   Colnot Céline C  

Stem cell reports 20200910 4


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<sup>Y637C/+</sup> over-activating mutation in Prx1-derived skeletal stem/progenitor cells leads to failure of fracture consolidation. We show that periosteal cells (PCs) carrying  ...[more]

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