Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.

• Project/Area Number: 26462287
• 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, 大学院医歯学総合研究科, 准教授 (90343152)
• Co-Investigator(Kenkyū-buntansha): 辻 邦和 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20323694) ; 宗田 大 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50190864) ; 関矢 一郎 東京医科歯科大学, 再生医療研究センター, 教授 (10345291)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 変形性膝関節症 / 動物モデル / 卵巣摘除 / トレッドミル / 滑膜炎症 / 関節軟骨 / 力学的負荷 / 滑膜炎 / Osteoarthritis / ovariectomy / forced running / synovitis / genetic background / 変性性関節症 / メカニカルストレス / 遺伝的背景

Outline of Final Research Achievements

Although osteoarthritis (OA) is a multifactorial disease, little is reported regarding the cooperative interaction between these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human post menopause condition. Histological analysis revealed that OVX or forced running respectively had subtle effect on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Interestingly, these results were observed specifically in Balb/c mice, since we did not observe any synergistic effects of OVX and forced running on articular cartilage degeneration in C57Bl/6J mice.
Since surgical procedure was not performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.

Research Products

• [Journal Article] Meniscal regeneration after resection of the anterior half of the medial meniscus in mice. (2017)
  • Author(s): Hiyama K, Muneta T, Koga H, Sekiya I, Tsuji K.
  • Journal Title: J Orthop Res. Volume: in press Issue: 9 Pages: 1958-1965
  • DOI: 10.1002/jor.23470
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Strenuous running exacerbates knee cartilage erosion induced by low amount of mono-iodoacetate in rats. (2017)
  • Author(s): Saito R, Muneta T, Ozeki N, Nakagawa Y, Udo M, Yanagisawa K, Tsuji K, Tomita M, Koga H, Sekiya I.
  • Journal Title: BMC Musculoskelet Disord. Volume: 18 Issue: 1 Pages: 36-36
  • DOI: 10.1186/s12891-017-1393-8
  • Peer Reviewed / Open Access
• [Journal Article] Effects of different cell detaching methods on the viability and cell surface antigen expression of synovial mesenchymal stem cells. (2017)
  • Author(s): Tsuji K, Ojima M, Otabe K, Horie M, Koga H, Sekiya I, Muneta T.
  • Journal Title: Cell Transplant. Volume: in press Issue: 6 Pages: 1089-1102
  • DOI: 10.3727/096368917x694831
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Centralization of extruded medial meniscus delays cartilage degeneration in rats. (2017)
  • Author(s): Ozeki N, Muneta T, Kawabata K, Koga H, Nakagawa Y, Saito R, Udo M, Yanagisawa K, Ohara T, Mochizuki T, Tsuji K, Saito T, Sekiya I.
  • Journal Title: J Orthop Sci. Volume: in press Issue: 3 Pages: 542-548
  • DOI: 10.1016/j.jos.2017.01.024
  • Peer Reviewed / Open Access
• [Journal Article] Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. (2016)
  • Author(s): Miyatake K, Muneta T, Ojima M, Yamada J, Matsukura Y, Abula K, Sekiya I, Tsuji K.
  • Journal Title: BMC Musculoskelet Disord. Volume: 17 Issue: 1 Pages: 238-238
  • DOI: 10.1186/s12891-016-1094-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Weekly injections of Hylan G-F 20 delay cartilage degeneration inpartial meniscectomized rat knees. (2016)
  • Author(s): Yanagisawa K, Muneta T, Ozeki N, Nakagawa Y, Udo M, Saito R, Koga H, Tsuji K, Sekiya I
  • Journal Title: BMC Musculoskelet Disord. Volume: 17 Issue: 1 Pages: 188-188
  • DOI: 10.1186/s12891-016-1051-6
  • Peer Reviewed / Open Access
• [Journal Article] Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates. (2016)
  • Author(s): Kondo S, Muneta T, Nakagawa Y, Koga H, Watanabe T, Tsuji K, Sotome S, Okawa A, Kiuchi S, Ono H, Mizuno M, Sekiya I
  • Journal Title: J Orthop Res Volume: in press Issue: 6 Pages: 1274-1282
  • DOI: 10.1002/jor.23211
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems. (2016)
  • Author(s): Udo M, Muneta T, Tsuji K, Ozeki N, Nakagawa Y, Ohara T, Saito R, Yanagisawa K, Koga H, Sekiya I.
  • Journal Title: Osteoarthritis Cartilage Volume: in press Issue: 7 Pages: 1284-91
  • DOI: 10.1016/j.joca.2016.02.005
  • Peer Reviewed / Open Access
• [Journal Article] Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats. (2016)
  • Author(s): Ozeki N, Muneta T, Koga H, Nakagawa Y, Mizuno M, Tsuji K, Mabuchi Y, Akazawa C, Kobayashi E, Matsumoto K, Futamura K, Saito T, Sekiya I
  • Journal Title: Osteoarthritis Cartilage Volume: in press Issue: 6 Pages: 1061-70
  • DOI: 10.1016/j.joca.2015.12.018
  • NAID: 40021330438
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age. (2015)
  • Author(s): Abula K, Muneta T, Miyatake K, Yamada J, Matsukura Y, Inoue M, Sekiya I, Graf D, Economides AN, Rosen V, Tsuji K.
  • Journal Title: FEBS Lett. Volume: in press Issue: 11 Pages: 197-200
  • DOI: 10.1016/j.febslet.2015.04.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Site-selective mott transition in a quasi-one-dimensional vanadate v_{6}o_{13}. (2015)
  • Author(s): Shimizu Y, Aoyama S, Jinno T, Itoh M, Ueda Y
  • Journal Title: Phys Rev Lett. Volume: 114
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Is Drain Tip Culture Prognostic of Surgical Site Infection? Results of 1380 Drain Tip Cultures in Total Hip Arthroplasty. (2015)
  • Author(s): Takada R, Jinno T, Koga D, Hirao M, Muneta T, Okawa A
  • Journal Title: J Arthroplasty. Volume: in press Issue: 8 Pages: 1407-1409
  • DOI: 10.1016/j.arth.2015.02.038
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Is closed suction drainage effective in early recovery of hip joint function? Comparative evaluation in one-stage bilateral total hip arthroplasty. (2015)
  • Author(s): Koyano G, Jinno T, Koga D, Hoshino C, Muneta T, Okawa A
  • Journal Title: J Arthroplasty. Volume: 30 Issue: 1 Pages: 74-8
  • DOI: 10.1016/j.arth.2014.08.007
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 低用量および高用量モノヨード酢酸を用いたラット膝関節炎疼痛モデルにおける疼痛行動評価及び組織学的検討 (2016)
  • Author(s): 星野傑、辻邦和、宇土美於、関矢一郎、宗田大
  • Organizer: 第9回 日本運動器疼痛学会
  • Place of Presentation: 御茶ノ水ソラシティーカンファレンスセンター、東京都千代田区
  • Year and Date: 2016-11-26
• [Presentation] モノヨード酢酸によるラット関節炎モデルにおいて炎症期の滑膜幹細胞投与の軟骨変性および疼痛に対する効果の検討 (2016)
  • Author(s): 宇土美於、辻邦和、星野傑、関矢一郎、宗田大
  • Organizer: 第9回 日本運動器疼痛学会
  • Place of Presentation: 御茶ノ水ソラシティーカンファレンスセンター、東京都千代田区
  • Year and Date: 2016-11-26
• [Presentation] 低用量モノヨード酢酸を用いたラット膝関節炎疼痛モデルにおける疼痛行動評価及び組織学的検討 (2016)
  • Author(s): 星野傑、辻邦和、宇土美於、関矢一郎、宗田大
  • Organizer: 第31回 日本整形外科基礎学術集会
  • Place of Presentation: 福岡国際会議場、福岡県福岡市
  • Year and Date: 2016-10-13
• [Presentation] 滑膜由来間葉系幹細胞を特徴付ける表面抗原の網羅的解析 (2016)
  • Author(s): 辻 邦和、尾島美代子、小田邉浩二、堀江雅史、古賀英之、関矢一郎、宗田 大
  • Organizer: 軟骨代謝学会
  • Place of Presentation: 広島県広島市、広島大学応仁会館
  • Year and Date: 2016-02-19
• [Presentation] 滑膜由来間葉系幹細胞を特徴付ける表面抗原の網羅的解析 (2015)
  • Author(s): 辻 邦和、尾島美代子、小田邉浩二、堀江雅史、古賀英之、関矢一郎、宗田 大
  • Organizer: 日本運動器移植、再生医学研究会
  • Place of Presentation: 山口県宇部市、ANAクラウンプラザホテル
  • Year and Date: 2015-09-25
• [Presentation] 変形性股 関節症の病態：寛骨臼形成不全とFAI (2014)
  • Author(s): 神野哲也, 古賀大介, 高田亮平, 平尾昌之, 星野ちさと, 小谷野岳, 森田定雄, 大川淳, 宗田大
  • Organizer: 第41 回日本股関節学会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2014-10-31
• [Presentation] Utility of muscle evoked potential monitoring in total hip arthroplasty. (2014)
  • Author(s): Daisuke Koga, Tetsuya Jinno, Shigenori Kawabata, Takeshi Muneta, Atsushi Okawa
  • Organizer: ICJR Pan Pacific Orthopaedic Congress
  • Place of Presentation: U.S.A.
  • Year and Date: 2014-07-16
• [Presentation] A case of pseudotumor after metal-on-highly cross-linked polyethylene bearing total hip arthroplasty. (2014)
  • Author(s): Akinobu Hyodo, Tetsuya Jinno, Daisuke Koga, Takeshi Muneta, Atsushi Okawa.
  • Organizer: 15th EFORT
  • Place of Presentation: U.K.
  • Year and Date: 2014-06-04
• [Presentation] Risk factors related to dislocation after primary total hip arthroplasty. (2014)
  • Author(s): Ryohei Takada, Tetsuya Jinno, Daisuke Koga, Masanobu Hirao, Chisato Hoshino, Yoshinori Asou, Sadao Morita, Takeshi Muneta, Atsushi Okawa.
  • Organizer: 15th EFORT
  • Place of Presentation: U.K.
  • Year and Date: 2014-06-04