G protein subunit β1 is an important mediator of the late stage of endochondral ossification
G protein subunit β1 is an important mediator of the late stage of endochondral ossification
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G蛋白亚基β1是软骨内骨化晚期的重要介质
DOI：
10.1016/j.bbrc.2020.08.119
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发表时间：
2020
影响因子：
3.1
通讯作者：
Nishimura Riko
中科院分区：
文献类型：
--
作者：
Ruengsinpinya Lerdluck;Murakami Tomohiko;Nakamura Eriko;Takahata Yoshifumi;Hata Kenji;Nakaminami Yuri;Okae Hiroaki;Nishimura Riko
G蛋白信号在骨骼发育中起着重要作用。G蛋白亚基β1（GNB 1）是G蛋白复合物的一个组成部分，与G蛋白信号传导相关。在人类中，GNB 1突变导致整体发育和持续性生长延迟以及严重的神经发育障碍。类似地，Gnb 1基因敲除（KO）小鼠显示具有神经管缺陷的生长迟缓。这些遗传研究提出了GNB 1调节骨骼发育的可能性。本研究旨在探讨GNB 1在Gnb 1-KO小鼠骨骼发育中的作用。Gnb 1-KO小鼠表现出侏儒、四肢缩短和长骨骨化带减少。原位杂交和RT-qPCR分析显示，Gnb 1-KO小鼠长骨中Col 10a 1和Mmp 13表达减少，而Runx 2、Osterix、Ihh、Gnb 1-KO来源的成骨细胞保持了钙化能力，成骨细胞标志基因的表达水平没有改变，提示成骨细胞分化和功能在Gnb 1-KO小鼠中不受影响。综上所述，我们的研究结果表明，GNB 1是通过调节Col 10a 1和Mmp 13的表达，在软骨内骨形成的晚期阶段所必需的。
G protein signaling plays important roles in skeletal development. G protein subunit β1 (GNB1) is a component of the G protein complex and is associated with G protein signaling. In humans,GNB1mutations cause global developmental and persistent growth delays and severe neurodevelopmental disability. Similarly,Gnb1-knockout (KO) mice display growth retardation with neural tube defects. These genetic studies raise the possibility that GNB1 regulates skeletal development. This study was designed to investigate the role of GNB1 in skeletal development usingGnb1-KO mice.Gnb1-KO mice showed dwarfism, shortening of limbs, and a decreased ossifying zone of long bones.In situhybridization and RT-qPCR analyses revealed thatCol10a1andMmp13expression was reduced in long bones ofGnb1-KO mice, whileRunx2,Osterix,Ihh, andPprexpression levels were similar to those in wild-type littermates.Gnb1-KO-derived osteoblasts maintained calcification abilities and the expression levels of osteoblast marker genes were unaltered, indicating that osteoblast differentiation and function were not affected inGnb1-KO mice. Taken together, our results show that GNB1 is required for the late stage of endochondral bone formation by regulatingCol10a1andMmp13expression.