Investigation of new osteoarthritis treatment targeting GREM1 induced by excessive mechanical stress loading.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16675
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Chang Song Ho 東京大学, 医学部附属病院, 助教 (80780551)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 変形性関節症 / 力学的ストレス / 軟骨代謝

Outline of Final Research Achievements

Japan is facing super-aged society, which no one have ever experienced. Osteoarthritis (OA) is a major problem which render large number of aged population disable, and deprive them of healthy normal life. Excessive mechanical stress is well known factor to induce OA. However, the pathomechanism of cartilage degradation under excessive mechanical loading remains unknown.
We found secretory protein GREM1 induced by excessive mechanical stress loading play a pivotal role to induce cartilage degradation via GREM1-VEGFR2-NFkB signaling pathway. Furthermore, we identified Rac1-NFkB signal to induce GREM1 under excessive mechanical stress loading in the joint cartilage. In the present study, we could look into the candidates of inhibitors,low-molecular compounds and neutralizing antibodies as new treatment of OA targeting GREM1.

Free Research Field

軟骨代謝、変形性関節症

Academic Significance and Societal Importance of the Research Achievements

過剰な力学的ストレスによって誘導される関節破壊因子GREM1をターゲットとした新規治療法の開発がもたらす国民の健康寿命の向上や医療経済への貢献は計り知れない。現在まで解明されていなかった過剰な力学的ストレスがOAを発症する機序の中で主要な役割を果たす因子が分泌蛋白であったという発見は学術的に興味深い知見であり、治療ターゲットが分泌蛋白という特性からレセプターの阻害因子、低分子化合物、中和抗体など様々な治療法の開発へと発展する可能性がある。本研究を足がかりとして有効な治療法が開発されれば、現在の侵襲的な手術療法やエビデンスが不十分な保存療法にとて変わる世界に先駆けた治療法となる可能性がある。