Journal of Bone and Mineral Metabolism

, Volume 30, Issue 3, pp 254–269 | Cite as

A fluorescence spotlight on the clockwork development and metabolism of bone

  • Tadahiro Iimura
  • Ayako Nakane
  • Mayu Sugiyama
  • Hiroki Sato
  • Yuji Makino
  • Takashi Watanabe
  • Yuzo Takagi
  • Rika Numano
  • Akira Yamaguchi
Review Article


Biological phenomena that exhibit periodic activity are often referred as biorhythms or biological clocks. Among these, circadian rhythms, cyclic patterns reflecting a 24-h cycle, are the most obvious in many physiological activities including bone growth and metabolism. In the late 1990s, several clock genes were isolated and their primary structures and functions were identified. The feedback loop model of transcriptional factors was proposed to work as a circadian core oscillator not only in the suprachiasmatic nuclei of the anterior hypothalamus, which is recognized as the mammalian central clock, but also in various peripheral tissues including cartilage and bone. Looking back to embryonic development, the fundamental architecture of skeletal patterning is regulated by ultradian clocks that are defined as biorhythms that cycle more than once every 24 h. As post-genomic approaches, transcriptome analysis by micro-array and bioimaging assays to detect luminescent and fluorescent signals have been exploited to uncover a more comprehensive set of genes and spatio-temporal regulation of the clockwork machinery in animal models. In this review paper, we provide an overview of topics related to these molecular clocks in skeletal biology and medicine, and discuss how fluorescence imaging approaches can contribute to widening our views of this realm of biomedical science.


Bone Molecular clock Imaging Circadian rhythms Feedback loop 



The authors express sincere thanks to Professor Tei H. at the Faculty of Natural System, Institute of Science and Engineering, Kanazawa University, for constructive support of our current research project. We would like thank Dr. Astushi Miyawaki and his colleagues at RIKEN, BSI for constructive discussions. We also thank Mr. Shin-ichiro Horie at Nikon Cooperation, Ms. Takayo Ito, Mr. Satoshi Takiguchi and Mr. Norio Ohba at Nikon Instech., Ltd., and Ms. Kayoko Suenaga at Carl Zeiss Micro Imaging for their expertise on microscopy and image processing. The current work was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology, Global Center of Excellence (GCOE) Program, “International Research Center for Molecular Science in Tooth and Bone Diseases” to T.I., A.N. and A.Y. T. I. was also supported in part by the Takeda Science Foundation, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research. T.I. and A.Y. were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS). M.S was supported by the RIKEN Junior Research Associate Program and a Grants-in-Aid for JSPS Fellows. R.N. was supported by the Global Center of Excellence (GCOE) Program, “Frontiers of Intelligent Sensing” program and the Chiyoda Health Foundation for Medical Research.

Conflict of interest

All authors have no conflicts of interest.


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2011

Authors and Affiliations

  1. 1.Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone DiseasesTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Section of Oral PathologyTokyo Medical and Dental UniversityTokyoJapan
  3. 3.Section of Developmental Oral Health SciencesTokyo Medical and Dental UniversityTokyoJapan
  4. 4.Section of Maxillofacial SurgeryTokyo Medical and Dental UniversityTokyoJapan
  5. 5.The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS)Toyohashi University of TechnologyToyohashiJapan
  6. 6.Laboratory of Genome and BiosignalTokyo University of Pharmacy and Life SciencesTokyoJapan
  7. 7.Laboratory for Cell Function and DynamicsBrain Science Institute, RIKENWako-cityJapan
  8. 8.Department of Orthopedic SurgeryJuntendo University Graduate School of MedicineTokyoJapan

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