An impact of CCN2-BMP-2 complex upon chondrocyte biology: evoking a signalling pathway bypasses ERK and Smads?

CCN family 2/connective tissue growth factor (CCN2/CTGF) is a secreted protein that regulates diverse cellular functions. In addition to being a growth factor to transmit mitogen-activated protein kinase (MAPK) signalling into cells, through largely unknown mechanism, CCN2 antagonizes bone morphogenetic proteins (BMPs) by direct interaction. CCN2 and BMPs co-localize in cartilage, and both of them promote proliferation and differentiation of chondrocytes in vivo and in vitro. However, it was unclear whether these growth factors act cooperatively, or mutually inhibitory in chondrocyte biology. In addition, an information whether the heterooligomer of CCN2 and BMPs has any physiological roles in skeletogenesis was completely missing. Takigawa and his colleagues have recently reported that CCN2 and BMP-2 interacted directly to mutually interfere with their downstream ERK and Smad signalling, whereas the CCN2-BMP-2 complex promoted chondrocyte differentiation [Maeda et al. (2009) J. Biochem. 145, 207-216]. This contradictory finding shed light on a possibility that the complex of CCN2 and BMP-2 is capable of activating an additional non-canonical signalling pathway to promote chondrocyte differentiation.