| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Osteonecrosis of the jaw (ONJ) is frequently reported as a major adverse effect induced by BP treatment. The RANKL inhibitor, denosumab, has been used to prevent SRE, but the frequency of ONJ induced by denosumab is similar to that by BPs. We therefore investigated the expression status of RANKL-inducible genes in zoledronate-treated mouse osteoclast precursor cells. Microarray analysis identified that the mRNA expression level of NFATc1 and CAII, was decreased in zoledronate-treated cells. Subsequent analyses verified that these two genes were significantly silenced by zoledronate and that their expression was restored following inhibition of zoledronate action by geranylgeraniol. Zoledronate inhibited RANKL-induced osteoclast differentiation by suppression of NFATc1 and CAII gene expression. Our results suggest that these genes might be common targets for zoledronate and denosumab in the mechanism underlying RANKL-induced osteoclast differentiation.
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