Screening for anti-arthralgic molecules derived from muscle

• Project/Area Number: 17K19715
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Saito Taku 東京大学, 医学部附属病院, 准教授 (30456107)
• Co-Investigator(Kenkyū-buntansha): 藤井 朋子 東京大学, 医学部附属病院, 特任助教 (40793089)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: 変形性関節症 / 関節痛 / 筋肉 / 整形外科学

Outline of Final Research Achievements

We performed forced running by treadmill to load mechanical stress on muscles around mouse knee joints, and optimized conditions. We used 12-week-old C57BL/6 male mice. We started the experiment after acclimatization for several days. We tested 5, 15, 25 m/min, for 15, 60 min/day, during 2 weeks, and adapted 25 m/min for 60 min/day because muscle volume was increased at maximum. We expression analyses using muscle samples from 0 and 2 weeks, and identified several molecules which were associated with inflammation.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症は、関節軟骨の変性に始まり、周辺の骨の硬化性変化、滑膜の炎症性変化を伴って進行し、関節痛を引き起こして運動機能を著しく低下させる疾患である。変形性関節症の患者は膝だけで国内に2,530万人も存在し、高齢化に伴ってその数は増え続けている。要支援、要介護の原因として社会的にも大きな損失をもたらしているが、保存治療にはいまだ有効な手段はない。変形性関節症患者に対して大腿四頭筋訓練を開始すると、筋力や筋量に変化が出る前に痛みが緩和されることは知られていたが、本研究ではその本態を見出した可能性があり、今後の創薬に繋がることが期待される。

Research Products

• [Journal Article] Excessive mechanical loading promotes osteoarthritis through the gremlin-1-NF-κB pathway. (2019)
  • Author(s): Chang Song Ho、Mori Daisuke、Kobayashi Hiroshi、Mori Yoshifumi、Nakamoto Hideki、Okada Keita、Taniguchi Yuki、Sugita Shurei、Yano Fumiko、Chung Ung-il、Kim-Kaneyama Joo-ri、Yanagita Motoko、Economides Aris、Canalis Ernesto、Chen Di、Tanaka Sakae、Saito Taku
  • Journal Title: Nat Commun. Volume: 10 Pages: 1442-1442
  • DOI: 10.1038/s41467-019-09491-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cooperation of PU.1 with IRF8 and NFATc1 defines chromatin landscapes during RANKL‐induced osteoclastogenesis (2019)
  • Author(s): Izawa Naohiro、Kurotaki Daisuke、Nomura Seitaro、Fujita Takanori、Omata Yasunori、Yasui Tetsuro、Hirose Jun、Matsumoto Takumi、Saito Taku、Kadono Yuho、Okada Hiroyuki、Miyamoto Takeshi、Tamura Tomohiko、Aburatani Hiroyuki、Tanaka Sakae
  • Journal Title: J Bone Miner Res. Volume: なし Pages: 1143-1154
  • DOI: 10.1002/jbmr.3689
  • Peer Reviewed / Open Access
• [Journal Article] Multi-layered PLLA-nanosheets loaded with FGF-2 induce robust bone regeneration with controlled release in critical-sized mouse femoral defects (2019)
  • Author(s): Murahashi Yasutaka、Yano Fumiko、Nakamoto Hideki、Maenohara Yuji、Iba Kousuke、Yamashita Toshihiko、Tanaka Sakae、Ishihara Kazuhiko、Okamura Yosuke、Moro Toru、Saito Taku
  • Journal Title: Acta Biomaterialia Volume: 85 Pages: 172-179
  • DOI: 10.1016/j.actbio.2018.12.031
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intra-articular administration of IκBα kinase inhibitor suppresses mouse knee osteoarthritis via downregulation of the NF-κB/HIF-2α axis (2018)
  • Author(s): Murahashi Yasutaka、Yano Fumiko、Kobayashi Hiroshi、Makii Yuma、Iba Kousuke、Yamashita Toshihiko、Tanaka Sakae、Saito Taku
  • Journal Title: Scientific Reports Volume: 8 Pages: 16475-16475
  • DOI: 10.1038/s41598-018-34830-9
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of gait parameters in a mouse model of surgically-induced knee osteoarthritis. (2018)
  • Author(s): Makii Y, Asaka M, Setogawa S, Fujiki S, Hosaka Y, Yano F, Oka H, Tanaka S, Fukui N, Yanagihara D, and Saito T
  • Journal Title: J Orthop Surg (Hong Kong) Volume: 印刷中
  • Peer Reviewed
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/