| Project/Area Number |
14370589
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
AOKI Kazuhiro Tokyo Medical and Dental University, Graduate School, Hard Tissue Engineering, Pharmacology, Assistant, 大学院・医歯学総合研究科, 助手 (40272603)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASAWA Toshiyuki Tokyo Medical and Dental University, Graduate School, Hard Tissue Engineering, Periodontology, Assistant, 大学院・医歯学総合研究科, 助手 (90262203)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | RANKL / vaccination / inflammatory bone destruction / ワクチン / 液性免疫 / 破骨細胞形成抑制 / 骨吸収抑制 / 歯周病モデル / 骨粗鬆症モデル / 関節リウマチモデル / タンパク製剤の問題点 / ワクチン療法 / TNF / CIAモデル |
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| Research Abstract |
Receptor activator of NF-kB ligand (RANKL) is a membrane-bound cytokine, which plays an important role in osteoclast differentiation and activation. We established a novel therapeutic approach against pathological bone resorption using RANKL vaccine. Administration of RANKL vaccine induced a rapid anti-RANKL antibody induction in mice, and efficiently suppressed bone destruction in arthritis model mice, SKG mice established by Dr Shimon Sakaguchi (Kyoto Univ.), and bone loss in ovariectomized mice.
The results of the studies reported here demonstrate that a therapeutic vaccine approach, targeting RANKL, is useful to inhibit bone destruction in pathological bone-loss conditions such as rheumatoid arthritis (RA) and osteoporosis. We could not show the effects of the vaccine on periodontal disease-model since we failed to establish the model. Although we could not make it this time, the effects of the vaccine on mice RA-model, a kind of the inflammatory bone destruction model, suggest the possibility for the inhibitory effects on bone destruction in periodontal disease.
Compared with the use of other therapeutic recombinant proteins against pathological antigens such as monoclonal antibodies, soluble receptor or other antagonists, a vaccine needs smaller doses of protein to induce its affect. Once the immune response is established by vaccination, it is easily maintained by boosting with the vaccine. The underlying pathology of bone destruction is similar in bone-related diseases such as RA, periodontitis and bone metastasis. This RANKL vaccination would be a novel approach to any kind of pathological bone destruction.
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