Hgs physically interacts with Smad5 and attenuates BMP signaling.

Signaling by members of the bone morphogenetic protein family plays a critical role in cartilage development and differentiation. Recently, the potential involvement of BMPs in the maintenance and repair of damaged adult articular cartilage has initiated an interest in the role of BMP signaling and the involved signaling pathways in the adult tissue. In this study, we identified Hgs as a novel Smad5 interactor using a cDNA expression library constructed from human adult cartilage. This interaction was confirmed by coimmunoprecipitation experiments in 293 EBNA cells and the chondrocytic cell line T/C-28a2. Overexpression of Hgs resulted in an attenuation of BMP-dependent transcriptional responses suggesting that Hgs acts as an inhibitor of BMP signaling. Of note, osteoarthritic chondrocytes which have been suggested previously to show increased reactivity to BMP-stimulation showed less expression of Hgs. Thus, it is tempting to speculate that both might be related to each other given the suppressive effect of BMP signaling on Hgs shown in this study.