2022 Fiscal Year Final Research Report
Immunological study of the effects of fungal secondary metabolite terrein on drug-related osteonecrosis of the jaw
Project/Area Number |
21K21087
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0907:Oral science and related fields
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2021-08-30 – 2023-03-31
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Keywords | 真菌二次代謝産物Terrein / MRONJ / 骨粗鬆症 |
Outline of Final Research Achievements |
The number of osteoporosis patients is increasing. Osteonecrosis of the jaw (MRONJ) is a major side effect of therapeutic drugs, and how to deal with it is a major problem in clinical dentistry. In this study, we investigated the effect of fungal secondary metabolite terrein on the pathogenesis of MRONJ, which is capable of regulating osteoclast differentiation through a mechanism different from that of existing drugs. Various test drugs were administered at the same time as the initiation of osteoporosis induction, and after tooth extraction in the 4th week, administration of the test drug was continued for an additional 4 weeks, and in the 8th week, the inflammatory status of the extracted tooth was evaluated by live imaging. After that, the maxilla and other bones were removed, and the condition of the hard tissue was evaluated by micro-CT. Tissue sections were prepared using samples after analysis, and the differentiation state of osteoclasts was evaluated by TRAP staining.
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Free Research Field |
歯科保存領域
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Academic Significance and Societal Importance of the Research Achievements |
我が国において,骨粗鬆症患者は年々増加している。骨粗鬆症の進行に伴い大腿骨近位部骨折や椎体骨折などが生じると,日常生活能力(ADL)が低下する大きな要因となる。骨粗鬆症の進行を抑制するために,BP製剤や抗RANKL抗体薬等の投与が推奨されているが,副作用として顎骨壊死(MRONJ)の発症があり,その対応が歯科臨床現場では大きな問題となっている。既存薬とは異なる機序で破骨細胞の分化誘導を制御しうる真菌二次代謝産物Terreinは,骨粗鬆症のみならずMRONJ発症を抑制する可能性がある。本研究成果により,今後の骨粗鬆症治療に新たな選択肢を提供できる可能性があり,学術的・社会的意義は高いと考える。
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