Authors: Su JL, Chiou J, Tang CH, et. al
Osteoporosis is one of the most common bone pathologies. A number of novel molecules has been reported to increase bone formation including cysteine rich protein 61 (CYR61), a ligand of integrin receptor, but mechanisms remain unclear. It is known that bone morphogenetic proteins (BMPs)-especially BMP-2-are crucial regulators of osteogenesis. However, the interaction between CYR61 and BMP-2 is unclear. We found that CYR61 significantly increases proliferation and osteoblastic differentiation in MC3T3-E1 osteoblasts and primary cultured osteoblasts. CYR61 enhances mRNA and protein expression of BMP-2 in time- and dose-dependent manner. Moreover, CYR61-mediated proliferation and osteoblastic differentiation are significantly decreased by knockdown of BMP-2 expression or inhibition of BMP-2 activity. In this study, we found integrin alphavbeta3 is critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We also found that ILK, which is downstream of the alphavbeta3 receptor, to be involved in CYR61-induced BMP-2 expression and subsequent osteoblastic differentiation through an ERK-dependent pathway. Taken together, our results show that CYR61 up-regulates BMP-2 mRNA and protein expression, resulting in enhanced cell proliferation and osteoblastic differentiation through activation of the alphavbeta3 integrin/ILK/ERK signaling pathway.