Elucidation of the regulatory mechanism of osteoclast migration into cortical bone

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K24056
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Okayama University of Science
• Principal Investigator: Kajikawa Shuhei 岡山理科大学, 獣医学部, 助教 (60846848)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: Profilin-1 / 破骨細胞 / 骨粗鬆症 / 分枝状アクチン線維

Outline of Final Research Achievements

Osteoporosis, which is caused by a disruption in the balance of bone metabolism, affects about one in ten people in Japan. While bisphosphonates are most commonly used for osteoporosis treatment, it has been reported that prolonged use of bisphosphonates lead to fractures in the femoral diaphysis, which is mainly composed of cortical bone. Therefore, regulatory mechanisms of osteoclast differentiation, function and migration in cortical bone urgently need to be elucidated.
In this study, we focused on Profilin-1, a regulator of actin polymerization, to analyze how osteoclast migration is regulated. Our data indicate Profilin-1 negatively controls osteoclast migration by suppressing the protrusive structures based on branched actin filaments and provides a new therapeutic target for osteopenia.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

加齢と切り離すことのできない骨粗鬆症は超高齢化社会にある日本では約10人に1人が罹患する。その治療にはビスホスホネート製剤がしばしば第一選択薬となるが、長期間の使用で主に皮質骨より構成される長管骨骨幹部の骨折リスクが上がることが知られており、未だ明確にされていない皮質骨量・質の制御機構解明が急がれている。本研究では皮質骨への破骨細胞浸潤制御に関わる可能性のある機構を明らかにし、骨量低下の新たな症治療ターゲット候補を提示した。