Comparison of β-adrenergic and glucocorticoid signaling on clock gene and osteoblast-related gene expressions in human osteoblast

Chronobiol Int. 2012 Feb;29(1):66-74. doi: 10.3109/07420528.2011.636496.


Most living organisms exhibit circadian rhythms that are generated by endogenous circadian clocks, the master one being present in the suprachiasmatic nuclei (SCN). Output signals from the SCN are believed to transmit standard circadian time to peripheral tissue through sympathetic nervous system and humoral routes. Therefore, the authors examined the expression of clock genes following treatment with the β-adrenergic receptor agonist, isoprenaline, or the synthetic glucocorticoid, dexamethasone, in cultured human osteoblast SaM-1 cells. Cells were treated with 10(-6) M isoprenaline or 10(-7) M dexamethasone for 2 h and gene expressions were determined using real-time polymerase chain reaction (PCR) analysis. Treatment with isoprenaline or dexamethasone induced the circadian expression of clock genes human period 1 (hPer1), hPer2, hPer3, and human brain and muscle Arnt-like protein 1 (hBMAL1). Isoprenaline or dexamethasone treatment immediately increased hPer1 and hPer2 and caused circadian oscillation of hPer1 and hPer2 with three peaks within 48 h. hPer3 expression had one peak after isoprenaline or dexamethasone treatment. hBMAL expression had two peaks after isoprenaline or dexamethasone treatment, the temporal pattern being in antiphase to that of the other clock genes. Dexamethasone treatment delayed the oscillation of all clock genes for 2-6 h compared with isoprenaline treatment. The authors also examined the expression of osteoblast-related genes hα-1 type I collagen (hCol1a1), halkaline phosphatase (hALP), and hosteocalcin (hOC). Isoprenaline induced oscillation of hCol1a1, but not hALP and hOC. On the other hand, dexamethasone induced oscillation of hCol1a1 and hALP, but not hOC. Isoprenaline up-regulated hCol1a1 expression, but dexamethasone down-regulated hCol1a1 and hALP expression in the first phase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / biosynthesis
  • CLOCK Proteins / genetics*
  • Cell Line
  • Circadian Rhythm
  • DNA Primers / chemistry
  • Dexamethasone / pharmacology
  • Gene Expression Regulation*
  • Glucocorticoids / metabolism*
  • Humans
  • Isoproterenol / pharmacology
  • Oscillometry / methods
  • Osteoblasts / metabolism*
  • Period Circadian Proteins / biosynthesis
  • Real-Time Polymerase Chain Reaction / methods
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, Glucocorticoid / metabolism*
  • Signal Transduction
  • Suprachiasmatic Nucleus / metabolism
  • Time Factors


  • ARNTL Transcription Factors
  • ARNTL protein, human
  • DNA Primers
  • Glucocorticoids
  • PER1 protein, human
  • PER2 protein, human
  • PER3 protein, human
  • Period Circadian Proteins
  • Receptors, Adrenergic, beta
  • Receptors, Glucocorticoid
  • Dexamethasone
  • CLOCK Proteins
  • CLOCK protein, human
  • Isoproterenol