Craniosynostosis-associated Fgfr2(C342Y) mutant bone marrow stromal cells exhibit cell autonomous abnormalities in osteoblast differentiation and bone formation.
Craniosynostosis-associated Fgfr2(C342Y) mutant bone marrow stromal cells exhibit cell autonomous abnormalities in osteoblast differentiation and bone formation.
复制标题
DOI：
10.1155/2013/292506
复制
发表时间：
2013
影响因子：
--
通讯作者：
Hatch NE
中科院分区：
文献类型：
--
作者：
Liu J;Kwon TG;Nam HK;Hatch NE
我们最近报道，Fgfr 2C 342 Y/+颅缝早闭小鼠的颅骨密度减少时，与野生型小鼠相比，从突变小鼠分离的颅骨细胞表现出抑制晚期成骨细胞分化。为了进一步支持颅缝早闭相关的Fgfr突变导致成骨细胞分化和矿化组织形成的细胞自主缺陷的观点，在这里，我们测试了从Fgfr 2C 342 Y/+小鼠分离的骨髓基质细胞分化成成骨细胞的能力。此外，为了确定Crouzon综合征的低骨量表型是否包括无骨骨骼，通过显微CT评估了长骨。Fgfr 2C 342 Y/+细胞在2D体外条件下培养时，在成骨细胞分化早期成骨基因表达增加，但碱性磷酸酶mRNA表达和酶活性降低，分化后期矿化减少。从Fgfr 2C 342 Y/+小鼠分离的细胞在体内3D基质中分化时也形成较少的骨。Fgfr 2C 342 Y/+小鼠长骨中的皮质骨参数降低。这些结果表明，Fgfr 2C 342 Y/+小鼠的骨髓基质细胞在成骨细胞分化和骨矿化方面具有自主缺陷，并且Fgfr 2C 342 Y突变影响轴骨和外骨骼。
We recently reported that cranial bones of Fgfr2C342Y/+ craniosynostotic mice are diminished in density when compared to those of wild type mice, and that cranial bone cells isolated from the mutant mice exhibit inhibited late stage osteoblast differentiation. To provide further support for the idea that craniosynostosis-associated Fgfr mutations lead to cell autonomous defects in osteoblast differentiation and mineralized tissue formation, here we tested bone marrow stromal cells isolated from Fgfr2C342Y/+ mice for their ability to differentiate into osteoblasts. Additionally, to determine if the low bone mass phenotype of Crouzon syndrome includes the appendicular skeleton, long bones were assessed by micro CT. Fgfr2C342Y/+ cells showed increased osteoblastic gene expression during early osteoblastic differentiation but decreased expression of alkaline phosphatase mRNA and enzyme activity, and decreased mineralization during later stages of differentiation, when cultured under 2D in vitro conditions. Cells isolated from Fgfr2C342Y/+ mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of Fgfr2C342Y/+ mice. These results demonstrate that marrow stromal cells of Fgfr2C342Y/+ mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the Fgfr2C342Y mutation influences both the axial and appendicular skeletons.
登录
查看更多内容
影响因子：
4.1
作者：
Chen, L;Li, D;Deng, CX
通讯作者：
Deng, CX
影响因子：
4.2
作者：
Liang, Guoying;Katz, Lee D.;Macica, Carolyn M.
通讯作者：
Macica, Carolyn M.
DOI：
10.3109/02844318109103433
发表时间：
1981-01-01
影响因子：
--
作者：
KREIBORG, S
通讯作者：
KREIBORG, S
DOI：
10.1002/ajmg.1320440121
发表时间：
1992-09-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
COHEN, MM;KREIBORG, S
通讯作者：
KREIBORG, S
影响因子：
6.2
作者：
Hatch, Nan E.;Li, Yan;Franceschi, Renny T.
通讯作者：
Franceschi, Renny T.