Development of Osteoporosis drugs for supramolecular micelles

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19224
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Terauchi Masahiko 東京医科歯科大学, 東京医科歯科大学病院, 助教 (10781742)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ポリロタキサン / 骨粗鬆症 / 破骨細胞 / ARONJ / 生体材料

Outline of Final Research Achievements

Bisphosphonates drugs have the potential to induce osteonecrosis of the jaw, i.e. anti-resorptive agents-related osteonecrosis of the jaw (ARONJ) is a recent issue. In this study, we aimed to develop an osteoporosis drug that does not induce ARONJ and designed a method to control osteoclast differentiation by regulating cholesterol using a supramolecular polyrotaxane (PRX). The effects of PRX on RANKL-induced biosynthesis of cholesterol and osteoclast differentiation in RAW264.7 cells were examined, and the results showed that PRX suppressed RANKL-induced biosynthesis of cholesterol and regulated osteoclast differentiation. Thus, PRX may be useful in the treatment of osteoporosis and other bone defects caused by osteoclast overactivity.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症や抗がん剤治療として用いられているビスフォスフォネート製剤や抗RANKL抗体の長期投与患者に対する抜歯などの歯科治療は顎骨壊死を誘発する、すなわちARONJが昨今の問題となっている。超分子構造を有するポリロタキサン（PRX）はこの特異構造により破骨細胞の分化に関連するコレステロールを除去することにより、破骨細胞の分化制御能を有することが確認できた。今後、本研究を継続することでARONJを惹起しない骨粗鬆症薬の開発を目指す。