Patophysiology of osteoarthritis

• Project/Area Number: 18K16629
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Okubo Naoki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60816578)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 変形性関節症 / 体内時計 / 時計遺伝子 / Cry / 概日リズム

Outline of Final Research Achievements

The circadian clock consists of some of clock genes. We identified suppression of circadian clock cryptochrome 2 promoted osteoarthritis.
Cry2 mRNA and protein were suppressed in mice with aging-related OA and with surgical OA models. Cry2 knock out (KO) but not Cry1 KO mice with experimental OA showed significantly increased severity of histopathological changes in cartilage.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症は、様々な要因が発症や進展に関与する多因子疾患であり、日本における罹病患者数は1000万人を超えるとされる。これまでに様々な要因が関与していることが明らかにされてきたが、体内時計についての研究は不十分であった。本研究では、体内時計を構成する時計遺伝子Cryが変形性関節症の抑制に関与していることを明らかにした。今後、さらなる研究を通して、病態解明や治療法の開発につなげられる可能性がある。

Research Products

• [Int'l Joint Research] The Scripps Research Institute(米国)
• [Journal Article] Suppression of circadian clock protein cryptochrome 2 promotes osteoarthritis (2020)
  • Author(s): Bekki H.、Duffy T.、Okubo N.、Olmer M.、Alvarez-Garcia O.、Lamia K.、Kay S.、Lotz M.
  • Journal Title: Osteoarthritis and Cartilage Volume: 28 Issue: 7 Pages: 966-976
  • DOI: 10.1016/j.joca.2020.04.004
• [Journal Article] REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output (2019)
  • Author(s): Ikeda Ryosuke、Tsuchiya Yoshiki、Koike Nobuya、Umemura Yasuhiro、Inokawa Hitoshi、Ono Ryutaro、Inoue Maho、Sasawaki Yuh、Grieten Tess、Okubo Naoki、Ikoma Kazuya、Fujiwara Hiroyoshi、Kubo Toshikazu、Yagita Kazuhiro
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 10171-10171
  • DOI: 10.1038/s41598-019-46656-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 変形性関節症におけるCRY2の発現低下 (2019)
  • Author(s): 大久保直輝、戸次 大史、Martin Lotz
  • Organizer: 第26回日本時間生物学会学術大会
• [Presentation] Suppression of circadian clock protein cryptochrome2 promotes osteoarthritis (2019)
  • Author(s): H Bekki, T Duffy, N Okubo, M Olmer, O Alvarez-Garcia, K Lamia, S Kay, M.K. Lotz
  • Organizer: Osteoarthritis research society international 2019
  • Int'l Joint Research