Endoglin is expressed on human chondrocytes and forms a heteromeric complex with betaglycan in a ligand and type II TGFbeta receptor independent manner.
Previous work has implicated transforming growth factor beta (TGFbeta) as an essential mediator of cartilage repair and TGFbeta signaling as a requirement for the maintenance of articular cartilage in vivo. However, the mechanisms regulating TGFbeta action in chondrocytes are poorly understood. Endoglin, an accessory receptor of the TGFbeta receptor superfamily, is highly expressed on endothelial cells and has been shown to potently modulate TGFbeta responses. It is not known whether chondrocytes express endoglin or whether it modulates TGFbeta signaling in these cells. In this study, we show that endoglin is expressed on human chondrocytes at levels comparable with endothelial cells and that it forms higher order complexes with the types I and II TGFbeta receptors. More importantly, we show that endoglin forms a heteromeric complex with betaglycan on these cells at endogenous receptor concentrations and ratios. Endoglin complexes with betaglycan in a ligand-independent and -dependent manner as indicated by co-immunoprecipitation in the absence of TGFbeta and after affinity labeling with radiolabeled TGFbeta, respectively. Also, the endoglin-betaglycan association can occur independently of the type II TGFbeta receptor. These findings, taken together with the available evidence that endoglin and betaglycan are potent modulators of TGFbeta signal transduction, imply that the complex formation between endoglin and betaglycan may be of critical significance in the regulation of TGFbeta signaling in chondrocytes.
Parker
Wendy L
WL
Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
Goldring
Mary B
MB
Philip
Anie
A
D015703:Antigens, CD; D015153:Blotting, Western; D002356:Cartilage / Q000378:metabolism; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D000071063:Endoglin; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000378:metabolism
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D008024:Ligands; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; C071736:betaglycan; D012313:RNA; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II