Fluid Flow-Induced Calcium Response in Osteoclasts: Signaling Pathways

Intracellular calcium oscillation and its downstream signaling in osteoclasts is believed to play critical roles in regulating bone resorption. Our previous study demonstrated that fluid shear stress (FSS) induced more calcium responsive peaks in the late differentiated osteoclasts than the early ones. In this paper, the signaling pathways of FSS-induced calcium response for the osteoclasts in different differentiation stages were studied. RAW264.7 macrophage cells were induced to differentiate into osteoclasts with the conditioned medium from MC3T3-E1 osteoblasts. Furthermore pharmacological agents were added to block the specific signaling pathways. Finally the cells were exposed to FSS at different levels (1 or 10 dyne/cm2) after being induced for 4 or 8 days. The results showed that the mechanosensitive, cation-selective channels, phospholipase C (PLC) and endoplasmic reticulum constituted the major signaling pathway for mechanical stimulation-induced calcium response in osteoclasts. Extracellular calcium or ATP involved with calcium oscillation in a FSS magnitude-dependent manner. This pathway study may help to give insight into the molecular mechanism of mechanical stimulation-regulated bone remodeling.