Self-sustained and entrainable circadian clock exists in the femur.

• Project/Area Number: 25861335
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MINAMI Yoichi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40415310)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 概日時計 / 発光イメージング / 軟骨 / 器官培養 / 体内時計 / 器官培養系 / 副甲状腺ホルモン / 大腿骨 / 同調

Outline of Final Research Achievements

We identified that the circadian clock exists in the femur using PER2::Luc knock-in mice. The bioluminescence obtained from organ cultured femur showed clear about 24-hr rhythms over 5days. In continuous culture, the circadian rhythm of the bioluminescence was observed over 9months. High- or low-magnification real-time bioluminescence microscopic imaging revealed that the robust circadian rhythms emanated from the articular cartilage and the epiphyseal cartilage within the growth plate. By adding forskolin or dexamethasone, the circadian clock was phase shifted in a stimulation time-dependent manner. These data strongly suggest that tissue-autonomous and entrainable circadian clock exists in the femur.
Parathyroid hormone (PTH) is a peptide hormone which plays important roles in bone metabolism. We found that PTH reset the circadian clock of the organ cultured femur. The PTH induced phase shift was occurred both dose-dependent and stimulation time-dependent manner.

Research Products

• [Journal Article] Parathyroid hormone resets the cartilage circadian clock of the organ-cultured murine femur. (2015)
  • Author(s): Okubo N, Fujiwara H, Minami Y, Kunimoto T, Hosokawa T, Umemura Y, Inokawa H, Asada M, Oda R, Kubo T, Yagita K.
  • Journal Title: Acta Orthopedica Volume: 13 Issue: 5 Pages: 1-5
  • DOI: 10.3109/17453674.2015.1029393
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prolonged bioluminescence monitoring in mouse ex vivo bone culture revealed persistent circadian rhythms in articular cartilages and growth plates. (2013)
  • Author(s): Okubo N, Minami Y, Fujiwara H, Umemura Y, Tsuchiya Y, Shirai T, Oda R, Inokawa H, Kubo T, Yagita K
  • Journal Title: PLoS One Volume: 8(11)
  • Peer Reviewed
• [Presentation] Parathyroid hormone, but not melatonin, resets the bone circadian clock. (2015)
  • Author(s): Okubo N, Minami Y, Fujiwara H, Kunimoto T, Hosokawa T, Oda R, Kubo T, Yagita K
  • Organizer: 61th Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: Las Vegas, United States
  • Year and Date: 2015-03-28 – 2015-03-31
• [Presentation] Prolonged Bioluminescence Monitoring in Mouse ex vivo Bone Culture Revealed Persistent Circadian Rhythms in Articular and Epiphyseal Cartilages (2014)
  • Author(s): Yoichi Minami, Naoki Okubo, Hiroyoshi Fujiwara, Ryo Oda, Toshikazu Kubo, Kazuhiro Yagita
  • Organizer: The Orthopaedic Research Society 2014 annual meeting
  • Place of Presentation: New Orleans, United States
• [Presentation] 骨組織には自律振動し同調能を持つ体内時計が内在している (2014)
  • Author(s): 南 陽一、大久保直輝、久保俊一、八木田和弘
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学郡元キャンパス
• [Presentation] 骨組織に自律振動し同調能を持つ体内時計が内在する (2013)
  • Author(s): 南 陽一
  • Organizer: 第19回「性と生殖」公開シンポジウム「人間科学における生命研究の最前線」
  • Place of Presentation: 早稲田大学国際会議場
  • Invited
• [Presentation] 骨組織には自律振動し同調能を持つ体内時計が内在している (2013)
  • Author(s): 南 陽一、大久保直輝、久保俊一、八木田和弘
  • Organizer: 第20回日本時間生物学会学術大会
  • Place of Presentation: 近畿大学東大阪キャンパス