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2018 Fiscal Year Final Research Report

Evaluation of potency of bone-protective candidates using various imaging technics.

Research Project

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Project/Area Number 16K11486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionOhu University

Principal Investigator

Suzuki Keiko  奥羽大学, 歯学部, 教授 (50119187)

Project Period (FY) 2016-04-01 – 2019-03-31
Keywords炎症性骨破壊 / イメージング / 骨代謝 / ビスホスホネート / アントシアニン / 抗酸化
Outline of Final Research Achievements

Bisphosphonates (BPs) have been widely used as anti-resorptive agents in metabolic bone diseases. MPMBP is a novel non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. Since inflammation is known to be a cause of the pathological bone resorption, we investigated the effects of MPMBP on bone metabolism using imaging technics. The results showed that: i) MPMBP increased the mRNA expression of ALP, COL-1, OCN, and BSP in MC3T3-E1 cells, ii) MPMBP inhibited the translocation of NF-κB/p65 to the nuclei in osteoblasts, iii) local injection of MPMBP to alveolar bone induced increases in both the bone mass and thickness of alveolar bone at the local site of injection in rabbits. Taken together, these findings suggest that MPMBP is a promising agent to prevent bone loss, or even accelerate new bone formation, through inducing an uncoupling between bone resorption and bone formation, which is preferable to maintain bone mass and quality.

Free Research Field

歯科薬理学

Academic Significance and Societal Importance of the Research Achievements

臨床現場で頻用されている第3世代ビスホスホネートは、強力な骨量増加作用をもつためにきわめて有用であるが、顎骨壊死・非定型大腿骨骨折などの重大な副作用が報告されている。本研究で新規開発を目指したMPMBPは抗酸化性側鎖をもつビスホスホネートであることから、NF-kappaB核移行抑制を介した骨芽細胞活性化により骨密度を上昇させるだけでなく、酸化ストレス軽減による骨質改善作用が認められた。すなわち、みずみずしく、しなやかな骨が形成されることが予想され、糖尿病や慢性腎不全患者にみられるような脆弱性骨折リスクをも減少させる全く新しいタイプの骨代謝疾患治療薬として臨床応用できる可能性が示唆された。

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Published: 2020-03-30  

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