| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Research Abstract |
It is widely accepted that mechanical loading is necessary to construct the architecture of bone and to maintain bone mass. However, the mechanism of how bone cells respond to mechanical stimuli is not known. To clarify this, we stimulated osteoblast-like MC3T3E1 cells by mechanical shaking of the culture dishes and found that the level of egr-1 gene, which is an early response gene and a transcription factor induced by growth factors or serum, increased 15 to 45 minutes after the shaking, with a peak at 30 minutes. The egr-1 gene elevation was not blocked by a prior exposure to indomethacin, saralasin, Rp-cAMP,A23187 and colchicine and it was blocked partially by cytochalasin D,H-7 and prolonged exposure to TPA.On the other hand, a prior incubation with cycloheximide, DRB,genistein, herbimycin A and BAPTA/AM completely blocked the egr-1 gene level enhanced by shaking culture dishes. Moreover, we found that in serum-deprived cells the egr-1 gene response to shaking was not induced. The addition of EGF,FGFb, LPA and TGFB1 into serum-free media did not rescue the egr-1 gene induction. These results suggested that the egr-1 gene response is regulated at the transcriptional level, and that it involves tyrosine kinase as well as labile or de novo protein, and requires a particular level of intracellular calcium and unkown serum factor (s).
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