A possible and novel treatment for osteoporosis by controlling the Frount signal pathway.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamagami Ryota 東京大学, 医学部附属病院, 助教 (00722191)
• Co-Investigator(Kenkyū-buntansha): 千々松 良太 東京大学, 医学部附属病院, 特任助教 (60803210) ; 矢野 文子 東京大学, 医学部附属病院, 届出研究員 (80529040) ; 寺島 裕也 東京大学, 医学部附属病院, 客員研究員 (90538729)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Frount / Disulfiram / osteoporosis / osteoclast / osteoarthritis

Outline of Final Research Achievements

Based on the data from recent sc RNA-seq and other findings, it has been suggested that macrophages play a significant role in the pathogenesis of osteoarthritis. It has also been reported that osteoclasts are the macrophage lineage cells, and that frount inhibitors impede the differentiation of osteoclasts in vitro. Taking these into consideration, we focused on the frount, a signal transduction factor that is common downstream of a part of chemokine signaling, which is one of the regulatory mechanisms of the macrophage function . We conducted verification to determine whether the use of inhibitors could improve the pathogenesis of osteoarthritis or osteoporosis. Both osteoarthritis and osteoporosis changes were improved. The detailed mechanism remains to be elucidated, though, the effect on osteoclasts is thought to be primary in osteoporosis.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症、変形性関節症は国内患者数が1280万人、2530万人と多く、骨粗鬆症は圧迫骨折や大腿骨近位部骨折などのリスクを上昇させることを介して、変形性関節症は直接関節機能の低下を介して、健常高齢者が要介護状態に至る前段階とされる「フレイル」とも密接な関係があるとされている。骨粗鬆症については既存の治療法が存在するが、投与期間に制限があることや否定形骨折などの合併症の問題もあり、変形性関節症については確固たる治療薬が存在しない。以上から、骨粗鬆症や変形性関節症に対する新たな治療法の確立は社会的に非常に意義が高いといえる。