Identification of genes induced by mechanical stress in osteocytes

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The mechanical stress is one of important factor to prevent osteoporosis and is considered to control bone resorption and formation. Osteocytes are most abundant cells in bone, and seem to more responsive to the mechanical stress than osteoblast or osteoclast. We investigated the genes relating to mechanical stress to reveal a role of mechanical stress in osteocytes.1. We identified cis-acting elements and trans-acting factors on 5' flanking regions of cyclooxygenase-2 gene stimulated by mechanical stress in MLO-Y4-A2 cells. NF-IL6, CREB, API were identified as trans-acting factors which bound to cis-acting elements of 5' flanking regions of cyclooxygenase-2 gene and induced cyclooxygenase-2 mRNA. These factors should be used as markers exploring machano-sensor of mechanical stress on plasma membrane of cells. (preparing for publication)2. We investigated the induction of parathyroid hormone (PTH) receptor by fluid shear stress in MLO-Y4-A2 osteocyte-like cells. When the fluid shear stress was exposed to MLO-Y4-A2 cells, PTH receptor mRNA was increased by about 6.2 times at 7 h analyzed by RT-PCR. Lusiferase assay with the promoter/enhancer domain considered the transcriptional regulation of PTH receptor by stress loading. The deletion analysis of promoter/enhancer domain revealed that the domain containing P1 region was correlated to the induction of PTH receptor. The fluid shear stress phosphorylated ERK-1 which was an up-stream signaling of COX-2 induction. However, PTH receptor induction was not inhibited by U-0126, ERK kinase inhibitor. These results suggested that the fluid shear stress was induced PTH receptor under transcriptional controls through a different signaling pathway from ERK/COX-2/PGE2. (preparing for publication)3. We identified other genes induced by mechanical stress, such as estrogen receptor α, CD44 antigen, ODF. We also identified some unidentified genes in MLO-Y4-A2 osteocyte-like cells. We have continued to analyzed these genes