Articular cartilage degradation induced by extensive treadmill exercise is greatly exacerbated by estrogen depletion in mice.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592206
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: JINNO Tetsuya 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (90343152)
• Co-Investigator(Kenkyū-buntansha): TSUJI Kunikazu 東京医科歯科大学, 医歯学総合研究科, 寄付講座准教授 (20323694) ; MUNETA Takeshi 東京医科歯科大学, 医歯学総合研究科, 教授 (50190864) ; SEKIYA Ichiro 東京医科歯科大学, 再生医療研究センター, 教授 (10345291)
• Project Period (FY): 2011 – 2013
• Keywords: 変形性関節症 / 関節軟骨 / メカニカルストレス / 卵巣摘除

Research Abstract

Osteoarthritis (OA) is considered to be a multifactorial disease with factors such as chronic inflammation, aging, menopause, obesity, genetic background, and mechanical stress. Estrogen depletion by ovariectomy (OVX) is reported to accelerate cartilage degradation in young female mice. Too much mechanical stress on articular cartilage, which may be caused by overweight, joint instability, or over-exercise, is reported to induce several catabolic factors for articular cartilage. These individual data clearly show that all these factors are involved in the pathogenesis of OA, however, orchestrated effects of these factors in OA progression are still unclear. To analyze the crosstalk between estrogen signal and mechanical stress on articular cartilage homeostasis, we analyzed the severity of cartilage damage after treadmill exercise in OVX mice. Here we reported that degree of articular cartilage degeneration induced by extensive treadmill exercise was greatly exacerbated by OVX.

Research Products

• [Journal Article] Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model (2014)
  • Author(s): Hatsushika, D., Muneta, T., Nakamura, T., Horie, M., Koga, H., Nakagawa, Y., Tsuji, K., Hishikawa, S., Kobayashi, E., and Sekiya, I.
  • Journal Title: Osteoarthritis Cartilage
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells in synovial fluid increase after meniscus injury (2014)
  • Author(s): Matsukura, Y., Muneta, T., Tsuji, K., Koga, H., and Sekiya, I.
  • Journal Title: Clin Orthop Relat Res Volume: 472 Pages: 1357-1364
  • Peer Reviewed
• [Journal Article] Meniscus regeneration by syngeneic, minor mismatched, and major mismatched transplantation of synovial mesenchymal stem cells in a rat model (2014)
  • Author(s): Okuno, M., Muneta, T., Koga, H., Ozeki, N., Nakagawa, Y., Tsuji, K., Yoshiya, S., and Sekiya, I.
  • Journal Title: J Orthop Res Volume: 32 Pages: 928-936
  • Peer Reviewed
• [Journal Article] Teneurin-4, a transmembrane protein, is a novel regulator that suppresses chondrogenic differentiation (2014)
  • Author(s): Suzuki, N., Mizuniwa, C., Ishii, K., Nakagawa, Y., Tsuji, K., Muneta, T., Sekiya, I., and Akazawa, C.
  • Journal Title: J Orthop Res Volume: 32 Pages: 915-922
  • Peer Reviewed
• [Journal Article] Ranges of active joint motion for the shoulder, elbow, and wrist in healthy adults (2013)
  • Author(s): Aizawa, J., Masuda, T., Hyodo, K., Jinno, T., Yagishita, K., Nakamaru, K., Koyama, T., and Morita, S.
  • Journal Title: Disabil Rehabil Volume: 35 Pages: 1342-1349
  • Peer Reviewed
• [Journal Article] Intraarticular injection of synovial stem cells promotes meniscal regeneration in a rabbit massive meniscal defect model (2013)
  • Author(s): Hatsushika, D., Muneta, T., Horie, M., Koga, H., Tsuji, K., and Sekiya, I.
  • Journal Title: J Orthop Res Volume: 31 Pages: 1354-1359
  • Peer Reviewed
• [Journal Article] Transplantation of aggregates of synovial mesenchymal stem cells regenerates meniscus more effectively in a rat massive meniscal defect (2013)
  • Author(s): Katagiri, H., Muneta, T., Tsuji, K., Horie, M., Koga, H., Ozeki, N., Kobayashi, E., and Sekiya, I.
  • Journal Title: Biochem Biophys Res Commun Volume: 435 Pages: 603-609
  • Peer Reviewed
• [Journal Article] Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells (2013)
  • Author(s): Miyatake, K., Tsuji, K., Yamaga, M., Yamada, J., Matsukura, Y., Abula, K., Sekiya, I., and Muneta, T.
  • Journal Title: Biochem Biophys Res Commun Volume: 431 Pages: 52-57
  • Peer Reviewed
• [Journal Article] Transplantation of Achilles tendon treated with bone morphogenetic protein 7 promotes meniscus regeneration in a rat model of massive meniscal defect (2013)
  • Author(s): Ozeki, N., Muneta, T., Koga, H., Katagiri, H., Otabe, K., Okuno, M., Tsuji, K., Kobayashi, E., Matsumoto, K., Saito, H., et al.
  • Journal Title: Arthritis Rheum Volume: 65 Pages: 2876-2886
  • Peer Reviewed
• [Journal Article] Isolation and characterization of multipotential mesenchymal cells from the mouse synovium (2012)
  • Author(s): Futami, I., Ishijima, M., Kaneko, H., Tsuji, K., Ichikawa-Tomikawa, N., Sadatsuki, R., Muneta, T., Arikawa-Hirasawa, E., Sekiya, I., and Kaneko, K.
  • Journal Title: PLoS One Volume: 7 Pages: e45517
  • Peer Reviewed
• [Journal Article] Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs (2012)
  • Author(s): Nakamura, T., Sekiya, I., Muneta, T., Hatsushika, D., Horie, M., Tsuji, K., Kawarasaki, T., Watanabe, A., Hishikawa, S., Fujimoto, Y., et al
  • Journal Title: Cytotherapy Volume: 14 Pages: 327-338
  • Peer Reviewed
• [Journal Article] Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis (2012)
  • Author(s): Sekiya, I., Ojima, M., Suzuki, S., Yamaga, M., Horie, M., Koga, H., Tsuji, K., Miyaguchi, K., Ogishima, S., Tanaka, H., et al.
  • Journal Title: J Orthop Res Volume: 30 Pages: 943-949
  • Peer Reviewed
• [Journal Article] Properties and usefulness of aggregates of synovial mesenchymal stem cells as a source for cartilage regeneration (2012)
  • Author(s): Suzuki, S., Muneta, T., Tsuji, K., Ichinose, S., Makino, H., Umezawa, A., and Sekiya, I.
  • Journal Title: Arthritis Res Ther Volume: 14 Pages: R136
  • Peer Reviewed
• [Journal Article] Osteopontin level in synovial fluid is associated with the severity of joint pain and cartilage degradation after anterior cruciate ligament rupture (2012)
  • Author(s): Yamaga, M., Tsuji, K., Miyatake, K., Yamada, J., Abula, K., Ju, Y.J., Sekiya, I., and Muneta, T.
  • Journal Title: PLoS One Volume: 7 Pages: e49014
  • Peer Reviewed
• [Journal Article] Comparison of different distal designs of femoral components and their effects on bone remodeling in 1-stage bilateral total hip arthroplasty (2012)
  • Author(s): Yamauchi, Y., Jinno, T., Koga, D., Asou, Y., Morita, S., and Okawa, A.
  • Journal Title: J Arthroplasty Volume: 27 Pages: 1538-1543
  • Peer Reviewed
• [Presentation] Articular cartilage degeneration and synovitis observed in the ovariectomized mice are greatly exacerbated by forced running (2013)
  • Author(s): Miyatake K, Tsuji, K, Yamada J, Matsukura Y, Kahaer A, Arai Y, Sekiya I,Muneta T
  • Organizer: 2013 Orthopaedic Research Society(ORS)
  • Place of Presentation: Henry B Gonzalez Convention Center, San Antonio (poster)
  • Year and Date: 2013-01-26
• [Presentation] Forced running (60km in 6wks) reverses bone and articular cartilage degeneration induced by ovariectomy in C57Bl/6 mice (2013)
  • Author(s): Yamada J,Tsuji K, Miyatake K, Matsukura Y,Kahar A,Arai Y,Sekiya I, Muneta T
  • Organizer: 2013 Orthopaedic Research Society(ORS)
  • Place of Presentation: Henry B Gonzalez Convention Center, San Antonio (poster)
  • Year and Date: 2013-01-26
• [Presentation] 変形性膝関節症に対する三次元歩行解析の有用性について (2012)
  • Author(s): 山田淳、辻邦和、宮武和正、松倉遊、Kahaer Abula、関矢一郎、宗田大
  • Organizer: 第5回日本運動器疼痛学会
  • Place of Presentation: 東京 (ポスター発表)
  • Year and Date: 2012-11-17
• [Presentation] C57Bl/6マウスにおいて6週60kmの走行負荷は卵巣摘除後の関節軟骨退行変性を抑制する (2012)
  • Author(s): 山田淳、辻邦和、宮武和正、松倉遊、Kahaer Abula、新井嘉則、大川淳、関矢一郎、宗田大
  • Organizer: 第27回日本整形外科学会基礎学術総会
  • Place of Presentation: 名古屋 (口演発表)
  • Year and Date: 2012-10-27
• [Presentation] 変形性関節症(OA)発症における卵巣摘除と強制走行の影響 (2012)
  • Author(s): 宮武和正、辻邦和、山田淳、松倉遊、Kahaer Abula、大川淳、関矢一郎、宗田大
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋 (ポスター発表)
  • Year and Date: 2012-10-26
• [Presentation] Articular cartilage degradation induced by extensive treadmill exercise is greatly exacerbated by estrogen depletion in mice (2012)
  • Author(s): Miyatake K, Tsuji K, Yamada M, Kahaer A, Matsukura Y, Sekiya I, Muneta T
  • Organizer: 2012 Osteoarthritis Research Society International(OARSI)
  • Place of Presentation: Barcelona , Spain (Poster)
  • Year and Date: 2012-04-26
• [Presentation] 変形性関節症(OA)発症における卵巣摘出と強制走行の影響 (2012)
  • Author(s): 宮武和正、辻邦和、山田淳、Kahaer Abula、松倉遊、関矢一郎、宗田大
  • Organizer: 第25回日本軟骨代謝学会
  • Place of Presentation: 名古屋 (ポスター発表)
  • Year and Date: 2012-03-09