Analysis of the role of mechanosensor-mediated JNK/p38 signaling in osteoimmunological regulation of osteoblasts

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In this study, we report that large-magnitude (12%) cyclic stretch induced Ca2+ influx in MC3T3-E1 osteoblasts, which subsequently activated ASK1 MAP3K. The activated ASK1-JNK lead to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, ASK1-p38 pathway induced expression of monocyte chemoattractant protein-3 (MCP-3) gene, which promoted chemotaxis of pre-osteoclasts. These results suggest that ASK1-JNK/p38 pathways contribute to the mechanism of mechanical overloading-induced bone resroption via cytokine-related gene expression.