2012 Fiscal Year Final Research Report
Analysis of acid extrusion mechanism through new regulatory protein during bone resorption
| Project/Area Number |
23890241
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Surgical dentistry
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | 骨代謝 / ビスホスホネート / 顎骨壊死 / 破骨細胞 / メバロン酸経路 |
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| Research Abstract |
The nitrogen-including bisphosphonates(NBP)-related osteonecrosis of the jaws (BRONJ)were suggested to be caused by the decrease in the substrates of prenylation includinggeranylgeranyl acid (GGOH) after treatment of NBPs. Then, in the present study, weexamined the effects of NBP zoledronic acid in presence or absence of the prenylationsubstrate GGOH on mouse osteoclast differentiation. The mouse bone marrowmacrophages was cultivated with or without GGOH in the presence of RANKL (80micro M) and zoledronic acid (7 micro M). To clarify the expression of target moleculesand osteoclast differentiation we performed these methods of TRAP staining, RT- andreal time-PCR and Western blot analysis in the treated cells. The zoledronic acidsuppressed the expression of TRAP the differentiation-related molecule, DC-STAMPand OC-STAMP the cell fusion-related molecules in bone marrow macrophages withRANKL treatment on dose-dependent manner. Furthermore, the zoledronic acidinhibited TRAP-positive multinuclear osteoclast differentiation. However, theincubation of zoledronic acid in the presence of GGOH restored the number ofTRAP-positive osteoclasts together with the recovery of the expression of TRAP,DC-STAMP and OC-STAMP. These results are suggested that NBPs may besuppressed the multi-nucleation in stage of osteoclast fusion. Furthermore, theprenylation substrates partially restored the suppression of osteoclast differentiation,suggesting in the prevention of BRONJ in the patients with treatment of NBPs.
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Research Products
(2 results)
