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The role of Collagen 6 in knee anterior cruciate ligament

Research Project

Project/Area Number 19K09581
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Nagao Masashi  順天堂大学, 革新的医療技術開発研究センター, 特任准教授 (50384110)

Co-Investigator(Kenkyū-buntansha) 伊豆 弥生  岡山理科大学, 獣医学部, 准教授 (90431949)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords前十字靭帯損傷 / 遺伝子 / 膝 / 靭帯損傷 / XII型コラーゲン / 12型コラーゲン / 前十字靭帯 / 前十字靱帯損傷 / 膝関節 / コラーゲン
Outline of Research at the Start

運動器の機能低下を防止するという観点から、前十字靭帯損傷における関連分子の機能を知ることが必要である。
本研究では我々のこれらの知見を元に、前十字靭帯における6型コラーゲンの機能を明らかとする予定である。

Outline of Final Research Achievements

Anterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures,100% functional recovery is unlikely. Several studies have reported an association between polymorphisms of the collagen XII gene COL12A1 and ACL rupture. Collagen XII is highly expressed in tendons and ligaments and regulates tissue structure and mechanical property. To elucidate the influence of collagen XII deficiency on ACL,4 to 19-week-old male Col12a1-/-(KO) and wild-type(WT) mice were used. The KO mice showed an abnormal gait with an 2.7-fold increase in step angle, suggesting altered step alignment. KO mice displayed 20-60% ACL discontinuities, but 0% discontinuity in the posterior cruciate ligament. No discontinuities were found in WT mice. Collagen XII mRNA expression in the ACL tended to decrease with aging. Our study demonstrates for the first time that collagen XII deficiency increases the risk of ACL injury.

Academic Significance and Societal Importance of the Research Achievements

スポーツ選手で一般的な膝外傷である前十字靭帯(ACL)損傷には一般的に手術療法が勧められている。様々な手術方法が提案されているが、スポーツ復帰までに最低半年間要する上に、怪我以前のパフォーマンスに戻れない事が多い。本研究では、ACL断裂におけるリスク因子としての12型コラーゲンが明らかになったことで、今後12型コラーゲンの遺伝子多型などでのリスク分析に繋がる可能性がある。本遺伝子の変異が明らかになっていれば選手へのリスクの説明や情報提供、トレーニングメニューの調整など可能となり、ACL損傷の予防に繋がる可能性のある研究である。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2023 2022 2021 2020 2019

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 18 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta‐analysis of randomized controlled trials2023

    • Author(s)
      Huang Wenbo、Nagao Masashi、Yonemoto Naohiro、Guo Sen、Tanigawa Takeshi、Nishizaki Yuji
    • Journal Title

      Pharmacoepidemiology and Drug Safety

      Volume: 32 Issue: 6 Pages: 671-684

    • DOI

      10.1002/pds.5594

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic Ability of a Smartphone App for Dry Eye Disease: Protocol for a Multicenter, Open-Label, Prospective, and Cross-sectional Study2023

    • Author(s)
      Nagino K、Okumura Y、Yamaguchi M、Sung J、Nagao M、Fujio K、Akasaki Y、Huang Ti、Hirosawa K、Iwagami M、Midorikawa-Inomata A、Fujimoto K、Eguchi A、Okajima Y、Kakisu Ki、Tei Y、Yamaguchi T、Tomida D、Fukui M、Yagi-Yaguchi Y、Hori Y、Shimazaki J、Nojiri S、Morooka Y、Yee A、Miura M、Ohno M、Inomata T
    • Journal Title

      JMIR Research Protocols

      Volume: 12 Pages: e45218-e45218

    • DOI

      10.2196/45218

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of the COVID-19 Pandemic on Injury Incidence in Japanese Male Professional Soccer Players2023

    • Author(s)
      Matsunaga Ryo、Nagao Masashi、Akagi Ryuichiro、Fukai Atsushi、Sando Takashi、Ikeda Hiroshi、Taketomi Shuji
    • Journal Title

      Orthopaedic Journal of Sports Medicine

      Volume: 11 Issue: 2 Pages: 232596712211493-232596712211493

    • DOI

      10.1177/23259671221149373

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cross-cultural adaptation, validity, reliability and responsiveness of the Japanese version of the Victorian Institute of sports assessment for patellar tendinopathy (VISA-P-J)2023

    • Author(s)
      Togashi Ishin、Nagao Masashi、Nishio Hirofumi、Nozu Shojiro、Shiota Yuki、Takazawa Yuji
    • Journal Title

      BMC Sports Science, Medicine and Rehabilitation

      Volume: 15 Issue: 1

    • DOI

      10.1186/s13102-023-00615-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Determining Optimal Intervals for In-Person Visits during Video-based Telemedicine in Patients with Hypertension: A Cluster Randomized Controlled Trial (Preprint)2022

    • Author(s)
      Nishizaki Yuji、Kuroki Haruo、Ishii So、Ohtsu Shigeyuki、Watanabe Chizuru、Nishizawa Hiroto、Nagao Masashi、Nojima Masanori、Watanabe Ryo、Sato Daisuke、Sato Kensuke、Kawata Yumi、Wada Hiroo、Toyoda Goichiro、Ohbayashi Katsumi
    • Journal Title

      JMIR Cardio

      Volume: - Pages: e45230-e45230

    • DOI

      10.2196/45230

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Grafting of autologous concentrated bone marrow processed using a point-of-care device for patients with osteonecrosis of the femoral head: A phase 1 feasibility and safety study2022

    • Author(s)
      Homma Yasuhiro、Masubuchi Yosuke、Shirogane Yuichi、Amano Hirofumi、Muramoto Yuko、Nagao Masashi、Okuno Ryuji、Baba Tomonori、Yamaji Ken、Tamura Naoto、Kaneko Kazuo、Ishijima Muneaki
    • Journal Title

      Regenerative Therapy

      Volume: 20 Pages: 18-25

    • DOI

      10.1016/j.reth.2022.03.002

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical efficacy of diquafosol sodium 3% versus hyaluronic acid 0.1% in patients with dry eye disease after cataract surgery: a protocol for a single-centre, randomised controlled trial2022

    • Author(s)
      Miura Maria、Inomata Takenori、Nojiri Shuko、Sung Jaemyoung、Nagao Masashi、Shimazaki Jun、Midorikawa-Inomata Akie、Okumura Yuichi、Fujio Kenta、Akasaki Yasutsugu、Kuwahara Mizu、Huang Tianxiang、Nakamura Masahiro、Iwagami Masao、Hirosawa Kunihiko、Fujimoto Keiichi、Murakami Akira
    • Journal Title

      BMJ Open

      Volume: 12 Issue: 1 Pages: e052488-e052488

    • DOI

      10.1136/bmjopen-2021-052488

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Individual characteristics and associated factors of hay fever: A large-scale mHealth study using AllerSearch2022

    • Author(s)
      Inomata Takenori、Nakamura Masahiro、Iwagami Masao、Sung Jaemyoung、Nakamura Masahiro、Ebihara Nobuyuki、Fujisawa Kumiko、Muto Kaori、Nojiri Shuko、Ide Takuma、Okano Mitsuhiro、Okumura Yuichi、Fujio Kenta、Fujimoto Keiichi、Nagao Masashi、Hirosawa Kunihiko、Akasaki Yasutsugu、Murakami Akira
    • Journal Title

      Allergology International

      Volume: 71 Issue: 3 Pages: 325-334

    • DOI

      10.1016/j.alit.2021.12.004

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice2021

    • Author(s)
      Fukusato Shin、Nagao Masashi、Fujihara Kei、Yoneda Taiju、Arai Kiyotaka、Koch Manuel、Kaneko Kazuo、Ishijima Muneaki、Izu Yayoi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 18 Pages: 4051-4051

    • DOI

      10.3390/jcm10184051

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Symptom‐based stratification for hay fever: A crowdsourced study using the smartphone application AllerSearch2021

    • Author(s)
      Inomata Takenori、Nakamura Masahiro、Iwagami Masao、Sung Jaemyoung、Nakamura Masahiro、Ebihara Nobuyuki、Fujisawa Kumiko、Muto Kaori、Nojiri Shuko、Ide Takuma、Okano Mitsuhiro、Okumura Yuichi、Fujio Kenta、Fujimoto Keiichi、Nagao Masashi、Hirosawa Kunihiko、Akasaki Yasutsugu、Murakami Akira
    • Journal Title

      Allergy

      Volume: 76 Issue: 12 Pages: 3820-3824

    • DOI

      10.1111/all.15078

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Projected numbers of knee and hip arthroplasties up to the year 2030 in Japan2021

    • Author(s)
      Matsuoka Hiroaki、Nanmo Hisayoshi、Nojiri Shuko、Nagao Masashi、Nishizaki Yuji
    • Journal Title

      Journal of Orthopaedic Science

      Volume: - Issue: 1 Pages: 161-166

    • DOI

      10.1016/j.jos.2021.09.002

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring urinary collagen metabolite changes following collagen peptide ingestion and physical activity using ELISA with anti active collagen oligopeptide antibody2021

    • Author(s)
      Osawa Yoshihiro、Nomura Kaho、Kimira Yoshifumi、Kushibe Seiji、Takeyama Ken-ichi、Nagao Masashi、Kataoka-Matsushita Aya、Koizumi Seiko、Mano Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13527-13527

    • DOI

      10.1038/s41598-021-92934-1

    • NAID

      120007150270

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Remnant preservation provides good clinical outcomes after anterior cruciate ligament reconstruction2021

    • Author(s)
      Huang Hui、Nagao Masashi、Nishio Hirofumi、Kaneko Haruka、Saita Yoshitomo、Takazawa Yuji、Ikeda Hiroshi、Kaneko Kazuo、Ishijima Muneaki
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: Jan 2 Issue: 11 Pages: 3763-3772

    • DOI

      10.1007/s00167-020-06406-6

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Validation and defining the minimal clinically important difference of the Japanese version of the IKDC Subjective Knee Form2021

    • Author(s)
      Huang Hui、Nagao Masashi、Arita Hitoshi、Nishio Hirofumi、Kaneko Haruka、Saita Yoshitomo、Ishijima Muneaki、Takazawa Yuji、Ikeda Hiroshi、Kaneko Kazuo
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 26 Issue: 1 Pages: 149-155

    • DOI

      10.1016/j.jos.2020.02.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reliability assessment of the functional movement screen for predicting injury risk in Japanese college soccer players2020

    • Author(s)
      Miyamori Takayuki、Nagao Masashi、Shimasaki Yu、Okazaki Takayuki、Akiyoshi Naoki、Nishio Hirofumi、Takazawa Yuji、Yoshimura Masafumi
    • Journal Title

      Journal of Physical Therapy Science

      Volume: 32 Issue: 12 Pages: 850-855

    • DOI

      10.1589/jpts.32.850

    • NAID

      130007953542

    • ISSN
      0915-5287, 2187-5626
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Platelet-rich plasma (PRP) accelerates murine patellar tendon healing through enhancement of angiogenesis and collagen synthesis2020

    • Author(s)
      Kobayashi Yohei、Saita Yoshitomo、Takaku Tomoiku、Yokomizo Tomomasa、Nishio Hirofumi、Ikeda Hiroshi、Takazawa Yuji、Nagao Masashi、Kaneko Kazuo、Komatsu Norio
    • Journal Title

      Journal of Experimental Orthopaedics

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1186/s40634-020-00267-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimal cutoff score for patient-reported outcome measures after anterior cruciate ligament reconstruction using load?displacement curve analysis2019

    • Author(s)
      Kim Sung-Gon、Nagao Masashi、Nozawa Masahiko、Doi Tokuhide
    • Journal Title

      Journal of Orthopaedic Surgery

      Volume: 27 Issue: 3

    • DOI

      10.1177/2309499019887581

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reproducibility, responsiveness and validation of the Tampa Scale for Kinesiophobia in patients with ACL injuries2019

    • Author(s)
      Huang H, Nagao M, Arita H, Shiozawa J, Nishio H, Kobayashi Y, Kaneko H, Nagayama M, Saita Y, Ishijima M, Takazawa Y, Ikeda H, Kaneko K
    • Journal Title

      Health Qual Life Outcomes

      Volume: 18 Issue: 1 Pages: 150-150

    • DOI

      10.1186/s12955-019-1217-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 6型、12型コラーゲンの膝前十字靱帯における機能解明2021

    • Author(s)
      福里 晋, 伊豆 弥生, 長尾 雅史, 石島 旨章
    • Organizer
      日本整形外科学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 膝前十字靱帯損傷における新たなリスク要因としてのXII型コラーゲンの機能の解明2020

    • Author(s)
      福里晋、長尾雅史
    • Organizer
      日本整形外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Collagen XII as a maintenance factor for anterior cruciate ligament2019

    • Author(s)
      福里晋、長尾雅史、伊豆弥生
    • Organizer
      アメリカ骨代謝学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膝前十字靭帯損傷における新たなリスク要因としてXII型コラーゲンの機能の解明2019

    • Author(s)
      福里晋、長尾雅史、伊豆弥生
    • Organizer
      日本骨代謝学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 膝前十字靭帯損傷における新たなリスク要因としてVI型およXII型コラーゲンの機能の解明2019

    • Author(s)
      福里晋、長尾雅史、伊豆弥生
    • Organizer
      日本整形外科学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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