FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair.
FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair.
复制标题
骨膜细胞中的FGFR3在骨修复中驱动软骨向骨转化。
DOI：
10.1016/j.stemcr.2020.08.005
复制
发表时间：
2020-10-13
影响因子：
5.9
通讯作者：
Colnot C
中科院分区：
文献类型：
--
作者：
Julien A;Perrin S;Duchamp de Lageneste O;Carvalho C;Bensidhoum M;Legeai-Mallet L;Colnot C
身体中的大多数器官和组织，包括骨骼，可以在损伤后修复，这是由于内源性成体干/祖细胞的激活来替换受损的组织。内源性干/祖细胞在骨骼修复疾病中的固有功能障碍仍然知之甚少。在这里，我们报告说，Fgfr 3 Y 637 C/+过度激活突变Prx 1衍生的骨骼干/祖细胞导致骨折巩固失败。我们发现携带Fgfr 3 Y 637 C/+突变的骨膜细胞（PC）可以参与成骨和软骨形成谱系，但移植后不发生终末软骨细胞肥大和转化为骨引起假关节。相反，Prx 1Cre; Fgfr 3 Y 637 C/+ PC引起纤维软骨和纤维化。相反，在Prx 1Cre; Fgfr 3 Y 637 C/+小鼠的骨折部位移植野生型PC允许肥大软骨向骨过渡并允许骨折巩固。因此，这些结果突出了软骨到骨的转化是骨修复的必要步骤，PC内的FGFR 3信号传导是这种转化的关键调节因子。骨骼干/祖细胞中的Fgfr 3 Y367 C激活突变阻止骨愈合;移植Prx 1Cre中的内在缺陷; Fgfr 3 Y 637 C/+ PC导致假关节Prx 1Cre; Fgfr 3 Y 637 C/+ PC不能支持软骨-骨转化野生型PC可以拯救Prx 1Cre; Fgfr 3 Y 637 C/+假关节表型Julien et al.报告了与Prx 1Cre; Fgfr 3 Y 637 C/+小鼠中的假关节和骨膜细胞（PC）功能损伤相关的严重骨修复表型。携带Fgfr 3 Y367 C激活突变的PC不能经历软骨-骨转化，从而揭示了该转化步骤在骨愈合中的重要作用。
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. Fgfr3Y367C activating mutation in skeletal stem/progenitor cells prevents bone healing Intrinsic deficiencies in transplanted Prx1Cre;Fgfr3Y637C/+ PCs cause pseudarthrosis Prx1Cre;Fgfr3Y637C/+ PCs cannot support cartilage-to-bone transformation Wild-type PCs can rescue the Prx1Cre;Fgfr3Y637C/+ pseudarthrosis phenotype Julien et al. report a severe bone repair phenotype associated with pseudarthrosis and functional impairment of periosteal cells (PCs) in Prx1Cre;Fgfr3Y637C/+ mice. PCs carrying the Fgfr3Y367C activating mutation cannot undergo cartilage-to-bone transformation thus uncovering an essential role of this transformation step in bone healing.
登录
查看更多内容
影响因子：
3.5
作者：
Jonquoy, Aurelie;Mugniery, Emilie;Legeai-Mallet, Laurence
通讯作者：
Legeai-Mallet, Laurence
影响因子：
6.2
作者：
O'Keefe, Regis J.;Tuan, Rocky S.;Schwarz, Edward M.
通讯作者：
Schwarz, Edward M.
DOI：
10.1016/j.bbadis.2008.11.010
发表时间：
2009-02-01
影响因子：
6.2
作者：
Pannier, Stephanie;Couloigner, Vincent;Legeai-Mallet, Laurence
通讯作者：
Legeai-Mallet, Laurence
影响因子：
4.6
作者：
Hu, Diane P.;Ferro, Federico;Bahney, Chelsea S.
通讯作者：
Bahney, Chelsea S.
影响因子：
14.8
作者：
Kusumbe，Anjali P.;Ramasamy，Saravana K.;Adams，Ralf H.
通讯作者：
Adams，Ralf H.