Verification of the usefulness of oxidative stress regulation for functional decline associated with age-related degeneration of locomotive organs

• Project/Area Number: 17K10942
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Juntendo University
• Principal Investigator: Nojiri Hidetoshi 順天堂大学, 医学部, 准教授 (10317456)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 運動器 / 酸化ストレス / GliSODin / スーパーオキシド / SOD / 健康食品 / サプリメント / SOD活性 / 変性 / 老化

Outline of Final Research Achievements

A double-blind, randomized trial of women aged 50 to 79 years with discomfort or pain in the knees and lower back was assigned to the GliSODin or placebo group and taken for 6 months to improve subjective symptoms and motor function. Analyzed. The placebo group has a locomotive syndrome 1: 5, locomotive syndrome 2:11, pre-locomotive: 6 people, GliSODin oral group is locomotive syndrome 1:10, locomotive syndrome 2:13, pre-locomotive: 1. The JKOM score tended to improve in the GliSODin group, but there was no significant difference. It is necessary to verify the effect of adjusting the bias of other evaluation items, and the analysis is currently underway.

Academic Significance and Societal Importance of the Research Achievements

我々は運動器における酸化ストレスがどう関わっているのか小動物を用いた基礎研究をベースに解明してきた。ヒトにおいても過剰な酸化ストレスを制御することにより運動器変性疾患の症状や機能改善が得られるものと期待される。今回、ヒト運動器組織における機能低下はSOD活性低下が原因であることが検証された。GliSODinの介入試験を行ったが、顕著な有意差を示すことができず投与期間、採取組織や評価方法などの課題が明確となった。厳密に研究対象に選択基準を設けたため、検者数が少なくなったこと、変性疾患への介入としては期間が短いことが要因と考えた。投与する抗酸化物質の選択、抗酸化制御の方法は今後の課題である。

Research Products

• [Journal Article] Association of Superoxide‐Induced Oxidative Stress With Rotator Cuff Tears in Human Patients (2019)
  • Author(s): Yoshida Keiichi、Itoigawa Yoshiaki、Wada Tomoki、Maruyama Yuichiro、Nojiri Hidetoshi、Kawasaki Takayuki、Kaneko Kazuo
  • Journal Title: Journal of Orthopaedic Research Volume: 38 Issue: 1 Pages: 212-218
  • DOI: 10.1002/jor.24472
  • Peer Reviewed / Open Access
• [Journal Article] Superoxide dismutase activity is significantly lower in end-stage osteoarthritic cartilage than non-osteoarthritic cartilage (2018)
  • Author(s): Koike M, Nojiri H, Kanazawa H, Yamaguchi H, Miyagawa K, Nagura N, Banno S, Iwase Y, Kurosawa H, Kaneko K.
  • Journal Title: PLoS One Volume: １３ Issue: 9 Pages: e0203944-e0203944
  • DOI: 10.1371/journal.pone.0203944
  • Peer Reviewed / Open Access
• [Journal Article] Apple procyanidins promote mitochondrial biogenesis and proteoglycan biosynthesis in chondrocytes. (2018)
  • Author(s): Masuda I, Koike M, Nakashima S, Mizutani Y, Ozawa Y, Watanabe K, Sawada Y, Sugiyama H, Sugimoto A, Nojiri H, Sashihara K, Yokote K, Shimizu T
  • Journal Title: Sci Rep. Volume: ８ Issue: 1 Pages: 7229-7229
  • DOI: 10.1038/s41598-018-25348-1
  • Peer Reviewed / Open Access
• [Journal Article] Antioxidant treatment with vitamin C attenuated rotator cuff degeneration caused by oxidative stress in Sod1-deficient mice. (2018)
  • Author(s): 30.Morikawa D, Nojiri H, Itoigawa Y, Ozawa Y, Kaneko K, Shimizu T.
  • Journal Title: JSES Open Access Volume: ２ Issue: 1 Pages: 91-96
  • DOI: 10.1016/j.jses.2017.11.003
  • Peer Reviewed / Open Access
• [Presentation] 末期膝OA患者の関節軟骨および滑膜におけるSOD活性とスーパーオキシドの挙動. (2017)
  • Author(s): 小池 正人, 野尻 英俊, 幡野 佐巳依, 宮川 慶, 澤 満美子, 岩瀬 嘉志, 黒澤 尚, 金子 和夫
  • Organizer: 第90回日本整形外科学会学術総会
• [Presentation] ロコモティブシンドロームと酸化ストレスの関連性～ロコモ初診時における横断研究 (2017)
  • Author(s): 幡野佐巳依, 野尻英俊, 小池正人, 宮川 慶, 澤 満美子, 岩瀬 嘉志, 黒澤 尚, 金子 和夫
  • Organizer: 第１７回日本抗加齢医学会総会
• [Presentation] 末期膝ＯＡにおけるＳＯＤ活性とスーパーオキシドの動向. (2017)
  • Author(s): 小池正人, 野尻英俊, 幡野佐巳依, 宮川 慶, 澤 満美子, 岩瀬 嘉志, 黒澤 尚, 金子 和夫
  • Organizer: 第１７回日本抗加齢医学会総会
• [Presentation] Imbalance between low sod activity and excessive superoxide occurs in end-stage OA cartilage and synovium. (2017)
  • Author(s): Koike M, Nojiri H, Banno S, Miyagawa K, Sawa M, Iwase Y, Kurosawa H, Kaneko K
  • Organizer: OARSI
  • Int'l Joint Research
• [Presentation] The relationship between locomotive syndrome and oxidative stress; Cross-sectional study of 66 patients with locomotive symptoms. (2017)
  • Author(s): Banno S, Nojiri H, Koike M, Miyagawa K, Iwase Y, Kurosawa H, Kaneko K
  • Organizer: Cell Symposia, Gothenburg, Sweden, May 21-23, 2017
  • Int'l Joint Research