The study for ATP biosynthesis in skeletal development and skeletal disorders

• Project/Area Number: 18H02922
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Gifu University
• Principal Investigator: Akiyama Haruhiko 岐阜大学, 大学院医学系研究科, 教授 (60402830)
• Co-Investigator(Kenkyū-buntansha): 河村 真吾 岐阜大学, 医学部附属病院, 助教 (30456511)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 骨格形成 / エネルギー代謝 / ミトコンドリア / 骨軟骨形成 / 嫌気性代謝 / 好気性 / 嫌気性 / Tfam / LDHA / AMPK / 好気性ATP生合成 / 嫌気性ATP生合成 / 骨軟骨 / 乳酸脱水素酵素A / ATP / 骨格 / ATP生合成 / 遺伝子改変マウス

Outline of Final Research Achievements

For analysis of the role of aerobic ATP production in skeletogenesis, we generated Tfam conditional knockout mice. These mice exhibited spontaneous bone fracture within a week after birth. In contrast, LDHA conditional knock out mice exhibited severe growth plate deformity. These data showed that during osteogenesis, aerobic ATP production by mitochondria is critical, and that during chondrogenesis, anaerobic ATP production is indispensable.

Academic Significance and Societal Importance of the Research Achievements

骨軟骨形成過程におけるエネルギー代謝の変化、すなわち好気性エネルギー代謝と嫌気性エネルギー代謝の精査は、胎性期の骨格異常疾患の研究に重要であるのみでなく、生後の骨粗鬆症や変形性関節症の病態解明及び新規治療法の開発にも大いに役立つ結果をもたらした。今後は、好気性エネルギー代謝及び嫌気性エネルギー代謝を亢進させる低分子化合物などの探索を行い、骨関節疾患における新規治療法の確立を目指す。