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Development of prophylactic treatment for rotator cuff degenerative rupture using antioxidants

Research Project

Project/Area Number 19K09622
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionKobe University

Principal Investigator

Mifune Yutaka  神戸大学, 医学部附属病院, 助教 (80608464)

Co-Investigator(Kenkyū-buntansha) 乾 淳幸  神戸大学, 医学部附属病院, 特命助教 (70457092)
西本 華子  神戸大学, 医学部附属病院, 特命助教 (30707154)
国分 毅  神戸大学, 医学研究科, 医学研究員 (40403266)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肩腱板断裂 / 抗酸化物質 / アポシニン / DHEA / NMN / 糖化最終生成物 / 活性酸素 / 肩腱板
Outline of Research at the Start

まずin vitro実験としてヒト腱板組織より肩腱板由来細胞を分離後、各種抗酸化薬の投与下で48時間培養し、酸化・炎症関連遺伝子の発現やROS・アポトーシスの発現、細胞活性など評価する。次にin vivo実験ではAGEs/ROS発現増強動物モデルとして 1年齢もしくは2年齢の高齢のラットまたは糖尿病ラットを用い、各種抗酸化薬を投与した上で、腱板組織におけるAGEs/ROS発現量および酸化・炎症関連遺伝子の発現、ROS・アポトーシスの発現量の評価、引っ張り試験による腱板強度評価を、抗酸化薬非投与群のラット腱板組織と比較検討する。

Outline of Final Research Achievements

We have previously reported that one of the age-related locomotor disorders, "non-traumatic (degenerative) rotator cuff tear," is associated with "oxidative and saccharification stress." This time, we aimed to develop a preventive treatment for rotator cuff tear mainly caused by degeneration using various antioxidants (aposinine, nicotinamide mononucleotide; NMN, dehydroepiandrosterone; DHEA). First, AGEs were added to rat Achilles tendon cells to apply glycation stress, and each antioxidant was administered, and its anti-glycation and antioxidant effects were confirmed. Also, in animal experiments, a rat Achilles tendon degeneration or inflammation model was created, and each antioxidant was administered to the model, and the degeneration or inflammation inhibitory effect was confirmed.

Academic Significance and Societal Importance of the Research Achievements

今回の結果から、肩腱板の変性の原因である糖化および酸化ストレスに対する治療薬として、アポシニン、NMN,DHEAが可能性のある薬剤であることが示唆され、今後の治療薬開発に対する一助になることが期待される。これにより、加齢とともに罹患率が上昇する肩腱板断裂の発生を抑えられることが期待される。しかし、現段階では、薬剤の投与方法が全身投与であることや、薬剤の副作用(全身に対する影響、局所に対する影響)に関して、まだ議論が必要であり、今後さらなる研究を進めることが必要である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Antioxidant effect of nicotinamide mononucleotide in tendinopathy2022

    • Author(s)
      Yamaura Kohei、Mifune Yutaka、Inui Atsuyuki、Nishimoto Hanako、Kurosawa Takashi、Mukohara Shintaro、Hoshino Yuichi、Niikura Takahiro、Kuroda Ryosuke
    • Journal Title

      BMC Musculoskeletal Disorders

      Volume: 23 Issue: 1

    • DOI

      10.1186/s12891-022-05205-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress2021

    • Author(s)
      Mukohara Shintaro、Mifune Yutaka、Inui Atsuyuki、Nishimoto Hanako、Kurosawa Takashi、Yamaura Kohei、Yoshikawa Tomoya、Kuroda Ryosuke
    • Journal Title

      BMC Musculoskeletal Disorders

      Volume: 22 Issue: 1

    • DOI

      10.1186/s12891-021-04398-z

    • NAID

      120007097076

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of apocynin in vitro on high glucose-induced oxidative stress on tenocytes2020

    • Author(s)
      Kurosawa Takashi、Mifune Yutaka、Inui Atsuyuki、Nishimoto Hanak、Ueda Yasuhiro、Kataoka Takeshi、Yamaura Kohei、Mukohara Shintaro、Kuroda Ryosuke
    • Journal Title

      Bone & Joint Research

      Volume: 9 Issue: 1 Pages: 23-28

    • DOI

      10.1302/2046-3758.991.bjr-2019-0074.r1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effectiveness of Dehydroepiandrosterone for high glucose-induced oxidative stress on rat Achilles tendon2021

    • Author(s)
      Mukohara S, Mifune Y, Inui A, Nishimoto H, et al.
    • Organizer
      2021 Annual meeting of Orthopaedic research society
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高血糖誘導酸化ストレスを与えた腱細胞に対するDHEAの効果2021

    • Author(s)
      向原伸太郎、美舩泰、乾敦幸、西本華子、他
    • Organizer
      第94回日本整形外科学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Apocynin for AGEs-induced oxidative stress2020

    • Author(s)
      Kurosawa T, Mifune Y, Inui A
    • Organizer
      2020 Annual meeting of Orthopaedic Research Society
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of Nicotinamide Mononucleotide, a Regulator of Aging for Anti-inflammatory and Anti-oxidative Effect in Tendinopathy2020

    • Author(s)
      Yamaura K, Mifune Y, Inui A
    • Organizer
      2020 Annual meeting of Orthopaedic Research Society
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of Dehydroepiandrosterone in vitro for high glucose-induced oxidative stress on tenocytes2020

    • Author(s)
      Mukohara S, Mifune Y, Inui A
    • Organizer
      2020 Annual meeting of Orthopaedic Research Society
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 老化制御因子NMN (Nicotinamide Mononucleotide)の腱炎に対する抗炎症・酸化作用の検討2020

    • Author(s)
      山裏耕平、美舩泰、乾淳幸
    • Organizer
      第93回日本形成外科学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 高血糖誘導酸化ストレスを与えた腱細胞に対するDHEAの効果2020

    • Author(s)
      向原伸太郎、美舩泰、乾淳幸
    • Organizer
      第93回日本形成外科学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Apocynin for AGEs-induced oxidative stress2020

    • Author(s)
      Takashi Kurosawa, Yutaka Mifune
    • Organizer
      2020 Orthopaedic Research Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] アポシニンは肩腱板由来細胞においてAdvanced glycation end-productsによる酸化ストレスに対して抑制効果を示す2019

    • Author(s)
      黒澤 堯、美舩 泰
    • Organizer
      第34回 日本整形外科学会基礎学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 終末糖化産物に対するアポシニンの抗酸化作用の検討2019

    • Author(s)
      黒澤 堯、美舩 泰
    • Organizer
      第46回 日本肩関節学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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