Elucidation of the development process of the cartilaginous biological clock

• Project/Area Number: 17K11021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kindai University (2018-2019); Kyoto Prefectural University of Medicine (2017)
• Principal Investigator: MINAMI Yoichi 近畿大学, 医学部, 助教 (40415310)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 軟骨 / 体内時計 / 発光イメージング / 概日リズム / 発光リズム / 器官培養 / 発達

Outline of Final Research Achievements

In this research project, the cartilaginous circadian clocks were studied. The obvious circadian rhythms of reporter gene activity were confirmed in both PERIOD2::Luciferase knock-in mouse and Per2-dLuc transgenic (TG) rats. When vertebral cartilage was collected and cultured from neonates and juvenile Per2-dLuc TG rats, peak phases of the bioluminescence rhythm were delayed according to age. These results suggest that not only mice but also rats are a good model for studying the cartilaginous circadian clock and the circadian clock phases are changes according to the cartilage development.

Academic Significance and Societal Importance of the Research Achievements

成長に伴う概日リズムのピーク時刻の変化は、他の臓器でも同様の知見が報告されているが、軟骨では初の知見である。今回、時計の分子機能を障害したラットでも同様の現象がみられたことは、この現象が軟骨の分化を反映する可能性を示唆している。軟骨の時計の研究には、マウスを実験モデルとして用いることが主流であったが、ラットは体長も大きく、外科的操作にも適した実験動物である。本研究から、軟骨の時計研究においても、ラットが有用なモデルであることが示された。

Research Products

• [Int'l Joint Research] マンチェスター大学(英国)
• [Journal Article] Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice (2020)
  • Author(s): Inokawa Hitoshi, Umemura Yasuhiro, Shimba Akihiro, Kawakami Eiryo, Koike Nobuya, Tsuchiya Yoshiki, Ohashi Munehiro, Minami Yoichi, Cui Guangwei, Asahi Takuma, Ono Ryutaro, Sasawaki Yuh, Konishi Eiichi, Yoo Seung-Hee, Chen Zheng, Teramukai Satoshi, Ikuta Koichi, Yagita Kazuhiro
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 2569-2569
  • DOI: 10.1038/s41598-020-59541-y
  • NAID: 120006799241
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circadian rhythms of soting nexin 25 in the mouse suprachiasmatic nucleus (2020)
  • Author(s): Takemura S, Nagano M, Isonishi A, Tanaka T, Tatsumi K, Yamano M, Minami Y, Shigeyoshi Y, Wanaka A
  • Journal Title: Neuroscience Letter Volume: 727 Pages: 134897-134897
  • DOI: 10.1016/j.neulet.2020.134897
  • Peer Reviewed
• [Journal Article] Slow shift of dead zone after an abrupt shift of the light-dark cycle (2019)
  • Author(s): Nagano Mamoru、Ikegami Keisuke、Minami Yoichi、Kanazawa Yuji、Koinuma Satoshi、Sujino Mitsugu、Shigeyoshi Yasufumi
  • Journal Title: Brain Research Volume: 1714 Pages: 73-80
  • DOI: 10.1016/j.brainres.2019.02.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chronic inflammation in mice exposed to the long-term un-entrainable light-dark cycles (2018)
  • Author(s): Minami Y, Ohashi M, Hotta E, Hisatomi M, Okada N, Konishi E, Teramukai S, Inokawa H, Yagita K.
  • Journal Title: Sleep Biol Rhythm Volume: 16 Issue: 1 Pages: 63-68
  • DOI: 10.1007/s41105-017-0127-5
  • NAID: 40021436060
  • Peer Reviewed
• [Presentation] Generation of a genetically modified rat overexpressing BMAL1 dominant negative form. (2020)
  • Author(s): Yoichi Minami, Tomoko Yoshikawa, Mamoru Nagano, Satoshi Koinuma, Kesuke Ikegami, Atsuko Fujioka, Keiichi Furukawa, Yasufumi Shigeyoshi.
  • Organizer: 第97回日本生理学会大会
• [Presentation] 新規体内時計異常モデルの開発を企図した遺伝子改変ラットの作出 (2019)
  • Author(s): 南 陽一、吉川朋子、長野護、鯉沼聡、池上啓介、藤岡厚子、重吉康史
  • Organizer: 第26回 日本時間生物学会学術大会
• [Presentation] 長期クロニックジェットラグ条件に曝露したマウスの継続的観察：概日リズムのマウスコホート研究の試み (2017)
  • Author(s): 南陽一，大橋宗洋，八木田和弘
  • Organizer: 第24回日本時間生物学会学術大会