The role of the XXXX signaling pathway in osteocyte mechanotransduction.

@entity1421 @entity5298 @entity15266 @entity460 @entity5596 @entity2159 @entity5595
UNASSIGNED: Osteocytes are proposed to be the mechanosensory cells that translate mechanical loading into biochemical signals during the process of bone adaptation. The lipid mediator @entity5595 ( @entity5596 ) has been reported to play a role in the mechanotransduction process of blood vessels and also in the dynamic control of bone mineral homeostasis. Nevertheless, the potential role of @entity5596 in bone mechanotransduction has yet to be elucidated. In this study, we hypothesized that a @entity5596 cascade is involved in the activation of osteocytes in response to loading-induced oscillatory fluid flow (OFF) in bone. MLO-Y4 osteocyte-like cells express the necessary components of a functional @entity5596 cascade. To examine the involvement of @entity5596 signaling in osteocyte mechanotransduction, we applied OFF (1Pa, 1Hz) to osteocyte-like MLO-Y4 cells under conditions where the @entity5596 signaling pathway was modulated. We found that decreased endogenous @entity5596 levels significantly suppressed the OFF-induced intracellular @entity460 response. Addition of extracellular @entity5596 to MLO-Y4 cells enhanced the synthesis and release of @entity1421 ( @entity1421 ) under static cells and amplified OFF-induced @entity1421 release. The stimulatory effect of OFF on the gene expression levels of @entity2159 ( @entity2159 ) and @entity5298 ( @entity5298 ) was @entity5596 dependent. Furthermore, the @entity15266 receptor subtype was shown to be involved in OFF-induced @entity1421 synthesis and release, as well as down-regulation of @entity5298 / @entity2159 gene expression ratio. In summary, our data suggest that @entity5596 cascade is involved in OFF-induced mechanotransduction in MLO-Y4 cells and that extracellular @entity5596 exerts its effect partly through @entity15266 receptors.
