Cellular mechanisms involved in mechanotransduction

摘要

Fluid flow induces increased c-fos and COX-2 expression in MC3T3-E1 cells that is dependent on flow-induced actin stress fiber formation (ASFF). The roles of intracellular Ca{sup}(2+) ([Ca{sup}(2+)]{sub}i) and Ca{sup}(2+) channels in theseresponses were examined using agents that alter [Ca{sup}(2+)]{sub}i. release and Ca{sup}(2+) entry. The intracellular Ca{sup}(2+) chelator, BAPTA, abolished flow-induced ASFF and gene expression, but Ca{sup}(2+) channel blockers, nifedipine andgadolinium, failed to inhibit these responses. Thapsigargin, which empties [Ca{sup}(2+)]{sub}i stores, and U73122, a phospholipase C inhibitor, completely suppressed flow-induced ASFF and c-fos/COX-2 expression. These data indicate that IP{sub}3-mediated[Ca{sup}(2+)]{sub}i release is essential for these flow induced responses in osteoblasts. However, we found that localization of Ca{sup}(2+) channels to the membrane was required for the [Ca{sup}(2+)]{sub}i response to flow in MC3T3-1 cells. Inhibition of these channels also reduced proliferation and increased alkaline phosphatase activity suggesting that these channels may be important to the differentiated state of osteoblastic cells.