Regulator of G-protein signaling (RGS) proteins differentially control chondrocyte differentiation.
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.
CIHR Group in Skeletal Development and Remodeling, Ontario, London, Ontario, Canada.
C Thomas G
CT
Appleton
Claudine G
CG
James
Frank
F
Beier
D000818:Animals; D002356:Cartilage / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics; D051379:Mice; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
D024043:Collagen Type II; D006609:High Mobility Group Proteins; D044162:Parathyroid Hormone-Related Protein; D020710:RGS Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D000242:Cyclic AMP