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, GNB1 mutations 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 using Gnb1-KO mice. Gnb1-KO mice showed dwarfism, shortening of limbs, and a decreased ossifying zone of long bones. In situ hybridization and RT-qPCR analyses revealed that Col10a1 and Mmp13 expression was reduced in long bones of Gnb1-KO mice, while Runx2, Osterix, Ihh, and Ppr expression 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 in Gnb1-KO mice. Taken together, our results show that GNB1 is required for the late stage of endochondral bone formation by regulating Col10a1 and Mmp13 expression.

G蛋白信号传导在骨骼发育中起重要作用。G蛋白亚基β1（GNB1）是G蛋白复合物的组成部分，与G蛋白信号传导相关。在人类中，GNB1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。同样，Gnb1基因敲除（KO）小鼠显示神经管缺陷的生长迟缓。这些基因研究提高了GNB1调节骨骼发育的可能性。这项研究旨在调查Gnb1- KO小鼠在骨骼发育中GNB1的作用。Gnb1- KO小鼠表现出侏儒症，四肢缩短和长骨骨化区减少。原位杂交和RT-qPCR的分析显示，COL10A1和MMP13表达在长骨减少GNB1 -KO小鼠，而Runx2的，Osterix的，Ihh信号，和PPR表达水平类似于在野生型同窝。GNB1 -KO衍生的成骨细胞的钙化保持能力和成骨细胞标志物基因的表达水平未改变，这表明成骨细胞分化和功能进行了不影响GNB1 -KO小鼠。综上所述，我们的结果表明，通过调节Col10a1和Mmp13表达。