The role of estradiol-mediated Nitric Oxide in the bone-repair process

• Project/Area Number: 18K09088
• 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: University of Occupational and Environmental Health, Japan
• Principal Investigator: Sabanai Ken 産業医科大学, 医学部, 非常勤医師 (70644863)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 一酸化窒素合成酵素 / NOS / 骨修復過程 / 骨折 / 性差 / 性ホルモン / エストラジオール / テストステロン / モデル動物 / 骨修復能 / Nitric Oxide / 骨代謝

Outline of Final Research Achievements

We investigated the role of estradiol (E2)-mediated Nitric Oxide (NO) in the cortical-bone-repair process using wild-type mice/triple Nitric Oxide Synthase (NOS) knockout mice after drill-hole injury. It was revealed in our study that cortical-bone repair depends on serum E2 concentration, and suggested that the anabolic effect of E2 on cortical-bone repair was mediated by NO. Further analysis will be conducted in the future.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会では骨折患者が増加し、医療経済的に大きな問題となる。骨粗鬆症治療による骨折予防も重要であるが、骨修復過程における調節因子の働きを理解してコントロールすることで骨折治癒期間を短縮できれば、早期に日常生活動作能を再獲得できる可能性がある。骨修復過程における性ホルモンを介した Nitric Oxide が果たす役割に関しては未だ解明されておらず、本研究成果については、社会的意義、学術的意義ともに大きいと考えている。

Research Products

• [Journal Article] Alpha-Defensin-1 in Synovial Fluid is Useful for Diagnosis of Joint Infection (2020)
  • Author(s): Takafumi TAJIMA, Toshiharu MORI, Fumitaka HIRANO, Ken SABANAI, Makoto KAWASAKI, Yoshiaki YAMANAKA, Manabu TSUKAMOTO, Akinori SAKAI
  • Journal Title: Journal of UOEH Volume: 42 Issue: 2 Pages: 167-173
  • DOI: 10.7888/juoeh.42.167
  • NAID: 130007852705
  • ISSN: 0387-821X, 2187-2864
  • Year and Date: 2020-06-01
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation (2020)
  • Author(s): Manabu Tsukamoto, Toshiharu Mori, Eiichiro Nakamura, Yasuaki Okada, Hokuto Fukuda, Yoshiaki Yamanaka, Ken Sabanai, Ke-Yong Wang, Takeshi Hanagiri, Satoshi Kuboi, Kazuhiro Yatera, Akinori Sakai
  • Journal Title: Osteoporosis and Sarcopenia Volume: 6 Issue: 4 Pages: 179-184
  • DOI: 10.1016/j.afos.2020.11.003
  • Peer Reviewed / Open Access
• [Journal Article] Effectiveness of regional clinical pathways on postoperative length of stay for hip fracture patients: A retrospective observational study using the Japanese Diagnosis Procedure Combination database (2020)
  • Author(s): Mine Yuko、Fujino Yoshihisa、Sabanai Ken、Muramatsu Keiji、Otani Makoto、Kubo Tatsuhiko、Fushimi Kiyohide、Matsuda Shinya
  • Journal Title: Journal of Orthopaedic Science Volume: 25 Issue: 1 Pages: 127-131
  • DOI: 10.1016/j.jos.2019.02.002
  • Peer Reviewed
• [Presentation] Smoothened阻害薬ソニデジブの腹腔内投与による椎間板変性と椎体骨棘形成の抑制効果 (2020)
  • Author(s): 福田北斗、中村英一郎、佐羽内研、塚本 学、田島貴文、岡田祥明、高田真一朗、山根宏敏、酒井昭典
  • Organizer: 第49回 日本脊椎脊髄病学会学術集会