Appleton C Thomas G, James Claudine G, Beier Frank
CIHR Group in Skeletal Development and Remodeling, Ontario, London, Ontario, Canada.
J Cell Physiol. 2006 Jun;207(3):735-45. doi: 10.1002/jcp.20615.
Control of chondrocyte differentiation is attained, in part, through G-protein signaling, but the functions of the RGS family of genes, well known to control G-protein signaling at the Galpha subunit, have not been studied extensively in chondrogenesis. Recently, we have identified the Rgs2 gene as a regulator of chondrocyte differentiation. Here we extend these studies to additional Rgs genes. We demonstrate that the Rgs4, Rgs5, Rgs7, and Rgs10 genes are differentially regulated during chondrogenic differentiation in vitro and in vivo. To investigate the roles of RGS proteins during cartilage development, we overexpressed RGS4, RGS5, RGS7, and RGS10 in the chondrogenic cell line ATDC5. We found unique and overlapping effects of individual Rgs genes on numerous parameters of chondrocyte differentiation. In particular, RGS5, RGS7, and RGS10 promote and RGS4 inhibits chondrogenic differentiation. The identification of Rgs genes as novel regulators of chondrogenesis will contribute to a better understanding of both normal cartilage development and the etiology of chondrodysplasias and osteoarthritis.
软骨细胞分化的控制部分是通过G蛋白信号传导实现的，但是RGS基因家族的功能在软骨形成过程中尚未得到广泛研究，该基因家族已知可在Gα亚基水平控制G蛋白信号传导。最近，我们已确定Rgs2基因是软骨细胞分化的调节因子。在此，我们将这些研究扩展到其他Rgs基因。我们证明，Rgs4、Rgs5、Rgs7和Rgs10基因在体外和体内软骨形成分化过程中受到不同的调控。为了研究RGS蛋白在软骨发育过程中的作用，我们在软骨形成细胞系ATDC5中过表达了RGS4、RGS5、RGS7和RGS10。我们发现单个Rgs基因对软骨细胞分化的众多参数具有独特且重叠的影响。特别是，RGS5、RGS7和RGS10促进软骨形成分化，而RGS4则抑制软骨形成分化。将Rgs基因鉴定为软骨形成的新型调节因子，将有助于更好地理解正常软骨发育以及软骨发育异常和骨关节炎的病因。
