Cellular mechanisms involved in mechanotransduction

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 Ca²⁺ ([Ca²⁺ ]) and Ca²⁺ channels in these responses were examined using agents that alter [Ca²⁺]_i, release and Ca ²⁺ entry. The intracellular Ca²⁺ chelator, BAPTA, abolished flow-induced ASFF and gene expression, but Ca²⁺ channel blockers, nifedipine and gadolinium, failed to inhibit these responses. Thapsigargin, which empties [Ca²⁺]_i, stores, and U73122, a phospholipase C inhibitor, completely suppressed flow-induced ASFF and c-fos/COX-2 expression. These data indicate that IP₃-mediated [Ca²⁺]_i release is essential for these flow induced responses in osteoblasts. However, the authors found that localization of Ca²⁺ channels to the membrane was required for the [Ca²⁺]i response to flow in MC3T3-E1 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