| Project/Area Number |
23792347
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgical dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 口腔外科学一般 / マイクロアレイ |
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| Research Abstract |
Objective. RANKL inhibitors, denosmab is recently available for use replace to bisphosphonates (BPs). However, the appearance frequency of osteonecrosis of jaw (ONJ) in denosmab treated patients is about the same as BPs. This evidence suggests that the inhibition of RANKL-mediated osteoclastogenesis may have close relationship with the outbreak of ONJ. According to this hypothesis, this study was designed to evaluate the effect of zoledronate on RANKL-mediated osteoclastogenesis and to investigate the molecular targets of zoledronate in RANKL-inducible genes. Methods. The direct effect of zoledronate on osteoclast differentiation was investigated using an in vitro culture system of osteoclast precursor cells stimulated with RANKL and M-CSF. The molecular targets of zoledronate in RANKL signal pathway and additional factors associated with osteoclastogenesis were analyzed by genome-widescreening. Results. Zoledronate reduced the formation of TRAP-positive multi-nucleated cells induced by RANKL treatment. Microarray analysis identified that 2 genes, nuclearfactor of activated T cells c1 (NFATc1) and carbonic anhydrase 2 (Car2), were silenced in zoledronate treated cells among RANKL-inducible genes and additional factors. Two genes, NFATc1 and Car2 were significantly silenced by zoledronate treatment. Conclusion. Zoledronate inhibited RANKL-mediated osteoclastogenesis. In addition, the expression of NFATc1 and Car2 is strongly suppressed by zoledronate. Our result suggests that these genes are possible targets of zolodronate in RANKL-mediated osteoclastogenesis
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