2010 Fiscal Year Final Research Report
Investigation of bone resorption by osteoclasts : aiming at therapy regulating osteoclastic bone resorption.
| Project/Area Number |
20590321
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Himeji Dokkyo University |
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Principal Investigator |
TOHYAMA Yumi Himeji Dokkyo University, 薬学部, 教授 (70362770)
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| Co-Investigator(Renkei-kenkyūsha) |
KAJI Hiroaki 姫路獨協大学, 薬学部, 講師 (10368706)
TANAKA Chisato 姫路獨協大学, 薬学部, 助手 (30461122)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 破骨細胞 / リソソーム |
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| Research Abstract |
Osteoclasts are bone-degrading cells playing an exclusive role in bone remodeling but molecular mechanism of osteolysis is poorly understood. Here we established a traceable and reproducible in vitro analyzing system for osteolysis using human osteoclasts because we found that an energy molecule ATP acts as a specific osteolysis initiator via P2X7-nucleotide receptor. We further show that deacetylation of α-tubulin is a critical reaction for osteolysis. Pharmacological inhibition of α-tubulin deacetylation resulted in defective bone resorption, accompanied by (1) failure of sealing-zone formation and (2) ceased secretion of osteolytic granules. Furthermore, kinetics of deacetylation was found to be regulated by Syk. These data suggest a novel P2X7-Syk-acetylation/deacetylation pathway for therapeutic targets in osteolytic diseases.
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