Prolonged bioluminescence monitoring in mouse ex vivo bone culture revealed persistent circadian rhythms in articular cartilages and growth plates

PLoS One. 2013 Nov 4;8(11):e78306. doi: 10.1371/journal.pone.0078306. eCollection 2013.

Abstract

The bone is a metabolically active organ which undergoes repeated remodeling cycles of bone resorption and formation. In this study, we revealed a robust and extremely long-lasting circadian rhythm in ex vivo culture maintained for over six months from the femoral bone of a PERIOD2(Luciferase) mouse. Furthermore, we also identified robust circadian clocks in flat bones. 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 of juvenile animals. Stimulation by forskolin or dexamethasone treatment caused type 0 phase resetting, indicating canonical entraining properties of the bone clock. Together, our findings from long-term ex vivo culture revealed that "tissue-autonomous" circadian rhythm in the articular cartilage and the growth plate of femoral bone functions for several months even in an organ culture condition, and provided a useful in vitro assay system investigating the role of the biological clock in bone formation or development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Colforsin / pharmacology
  • Dexamethasone / pharmacology
  • Female
  • Femur / drug effects
  • Femur / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter
  • Growth Plate / drug effects
  • Growth Plate / metabolism*
  • Luciferases / genetics*
  • Luciferases / metabolism
  • Luminescent Measurements
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Imaging
  • Period Circadian Proteins / genetics*
  • Period Circadian Proteins / metabolism
  • Tissue Culture Techniques

Substances

  • Period Circadian Proteins
  • Colforsin
  • Dexamethasone
  • Luciferases

Grants and funding

This work was supported in part by PRESTO Program of the Japan Science and Technology Agency (K.Y.), and by JSPS KAKENHI Grant Number 23390051 (K.Y.) and 25861335 (Y.M.). This work was also supported by the Takeda Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.