Loading of Mechanical Stress to Osteoblasts May Induce Cytokine Cross Talks between Osteoblasts and Monocytes/Macrophages in a JNK/p38-dependent Manner

Although mechanical stress has been shown to regulate bone modeling and remodeling, the mechanisms of bone remodeling after mechanical stress loading are not fully understood. We previously investigated the effects of loading of cyclic mechanical stretch on the activaties of JNK and p38 in MC3T3-E1 osteoblastic cells, and observed that JNK and p38 were activated by the mechanical stress. The patterns of their activation differed depending on the magnitude and duration of mechanical stress. In this study, we performed DNA microarray and quantitative RT-PCR analyses to investigate the biological outputs induced by activation of JNK and p38. We observed that expression of a number of genes was induced by mechanical stress-ehnanced activation of JNK and p38. One of these genes was osteoprotegerin which is a major bone metabolism related gene. The list of the genes also included Fn14monocyte, a cytokine receptor family member whose ligand had been known to be produced by monocytes and macrophages, and monocyte chemoattractant protein-3. These data suggests that mechanical stress-activated JNK and p38 induce cytokine cross talks between osteoblasts and bone marrow-derived monocytes and macrophages, which may play key roles in bone remodeling.