The development of novel osteoporosis drug for the super aging society -Application of low molecular compound, terrein-

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17069
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Okayama University
• Principal Investigator: Nakagawa Saki 岡山大学, 歯学部, 客員研究員 (60814522)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: テレイン / 骨粗鬆症 / 破骨細胞

Outline of Final Research Achievements

The small molecule terrein, a fungal metabolite, potently suppressed the expression of NFATc1, a major factor in RANKL-induced osteoclast differentiation, in mouse bone marrow-derived macrophage cells and suppressed osteoclast differentiation. It was suggested that NFATc1 expression may be repressed by a pathway other than the previously reported signaling pathway.
Intraperitoneal administration of terrein to a mouse model of osteoporosis significantly inhibited femoral resorption. It was also confirmed that terrein-treated mice showed low biotoxicity, such as hepatic renal impairment.

Free Research Field

歯周病学、歯内療法学

Academic Significance and Societal Importance of the Research Achievements

今回の研究において、低分子化合物terreinは既存薬とは異なる機序で骨吸収を抑制する可能性が示唆された。ビスフォスフォネート（BP）製剤等の既存の骨粗鬆症治療薬には、薬剤関連性顎骨壊死（MRONJ）などの重篤な副作用がある。Terreinは、BP製剤とは異なる機序で骨破壊を抑制できうる可能性があり、より重篤な副作用の少ない治療薬として応用できる可能性が示唆される。