Circadian regulation of bone metabolism by β-adrenergic signaling, glucocorticoids, and clock genes

Publication date: Available online 14 October 2014 Source:Journal of Oral Biosciences Author(s): Hisataka Kondo , Akifumi Togari Circadian rhythms have been identified in bone metabolism. However, the molecular mechanisms involved are poorly understood. It was recently reported that circadian rhythms are regulated by clock genes. The main circadian rhythms are generated by endogenous circadian clocks in suprachiasmatic nuclei (SCN). Recently, we reported that output signals from the SCN are transmitted from the master circadian rhythm to peripheral osteoblasts and osteoclasts through β-adrenergic signaling and/or glucocorticoids. Treatment with a β-agonist and synthetic glucocorticoid synchronized clock and osteoblast-related genes in cultured human osteoblasts. On the other hand, treatment with dexamethasone, but not β-agonist, synchronized clock and osteoclast-related genes in cultured mouse osteoclasts. Chromatin immune-precipitation (ChIP) assay showed the interaction between brain and muscle Arnt-like protein (BMAL) and the promoter regions of osteoclast related genes such as cathepsin K (CTSK) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). To examine whether endogenous glucocorticoid influences the circadian rhythms of bone metabolism, mice were adrenalectomized (ADX) or sham operated. These mice were maintained under a 12-hour light/dark cycle for two weeks and mRNA was collected from the femur, every 4 hours for a 24-hr period. In sham operat...
Source: Journal of Oral Biosciences - Category: Biomedical Science Source Type: research