Compressive force-produced CCN2 induces osteocyte apoptosis through ERK1/2 pathway

Osteocytes produce various factors in response to mechanical stimuli. One such factor, CCN2 is thought to play a significant role in osteocyte responses to mechanical stimuli, but its function in osteocytes is not well understood. We analyzed chick osteocyte response to compressive force focusing on apoptosis and CCN2 by using our original culture device that can apply quantitative mechanical stimuli. Compressive force increased CCN2 gene expression and protein production, and induced apoptosis in osteocytes. Application of exogenous CCN2 protein induced apoptosis, and a neutralizing CCN2 antibody blocked loading-induced apoptosis. We further examined how CCN2 induce apoptosis in loaded osteocytes. In loaded osteocytes, ERK1/2 was phosphorylated, and an ERK1/2 inhibitor blocked loading-induced apoptosis. Application of exogenous CCN2 protein caused ERK1/2 phosphorylation, and the neutralizing CCN2 antibody inhibited loading-induced ERK1/2 phosphorylation. These results demonstrated that enhanced production of CCN2 in osteocytes under compressive force loading induces apoptosis through ERK1/2 pathway.