Endoglin Is Expressed on Human Chondrocytes and Forms a Heteromeric Complex With Betaglycan in a Ligand and Type II TGFβ Receptor Independent Manner

• Published in: Journal of bone and mineral research 2003-02, Vol.18 (2), p.289-302
• Main Authors: Parker, Wendy L, Goldring, Mary B, Philip, Anie
• Format: Article
• Language: English
• Subjects: betaglycan; Biological and medical sciences; cartilage; chondrocytes; endoglin; Fundamental and applied biological sciences. Psychology; Skeleton and joints; transforming growth factor β receptors; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2003.18.2.289

Previous work has implicated transforming growth factor β (TGFβ) as an essential mediator of cartilage repair and TGFβ signaling as a requirement for the maintenance of articular cartilage in vivo. However, the mechanisms regulating TGFβ action in chondrocytes are poorly understood. Endoglin, an accessory receptor of the TGFβ receptor superfamily, is highly expressed on endothelial cells and has been shown to potently modulate TGFβ responses. It is not known whether chondrocytes express endoglin or whether it modulates TGFβ 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 TGFβ 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 TGFβ and after affinity labeling with radiolabeled TGFβ, respectively. Also, the endoglin‐betaglycan association can occur independently of the type II TGFβ receptor. These findings, taken together with the available evidence that endoglin and betaglycan are potent modulators of TGFβ signal transduction, imply that the complex formation between endoglin and betaglycan may be of critical significance in the regulation of TGFβ signaling in chondrocytes.