Review Article

Journal of Bone and Mineral Metabolism

, Volume 30, Issue 3, pp 254-269

First online:

A fluorescence spotlight on the clockwork development and metabolism of bone

  • Tadahiro IimuraAffiliated withGlobal Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental UniversitySection of Oral Pathology, Tokyo Medical and Dental University Email author 
  • , Ayako NakaneAffiliated withGlobal Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental UniversitySection of Oral Pathology, Tokyo Medical and Dental UniversitySection of Developmental Oral Health Sciences, Tokyo Medical and Dental University
  • , Mayu SugiyamaAffiliated withSection of Oral Pathology, Tokyo Medical and Dental UniversityLaboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life SciencesLaboratory for Cell Function and Dynamics, Brain Science Institute, RIKEN
  • , Hiroki SatoAffiliated withSection of Oral Pathology, Tokyo Medical and Dental University
  • , Yuji MakinoAffiliated withSection of Oral Pathology, Tokyo Medical and Dental UniversityDepartment of Orthopedic Surgery, Juntendo University Graduate School of Medicine
  • , Takashi WatanabeAffiliated withGlobal Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental UniversitySection of Oral Pathology, Tokyo Medical and Dental UniversitySection of Maxillofacial Surgery, Tokyo Medical and Dental University
  • , Yuzo TakagiAffiliated withSection of Developmental Oral Health Sciences, Tokyo Medical and Dental University
  • , Rika NumanoAffiliated withThe Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology Email author 
  • , Akira YamaguchiAffiliated withGlobal Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental UniversitySection of Oral Pathology, Tokyo Medical and Dental University Email author 

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Abstract

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.

Keywords

Bone Molecular clock Imaging Circadian rhythms Feedback loop