Circadian Oscillation of Gene Expression in Murine Calvarial Bone

Abstract

ABSTRACT:The genes encoding the core circadian transcription factors display an oscillating expression profile in murine calvarial bone. More than 26% of the calvarial bone transcriptome exhibits a circadian rhythm, comparable with that observed in brown and white adipose tissues and liver. Thus, circadian mechanisms may directly modulate oxidative phosphorylation and multiple metabolic pathways in bone homeostasis.Introduction: Although circadian rhythms have been associated historically with central regulatory mechanisms, there is emerging evidence that the circadian transcriptional apparatus exists in peripheral tissues. The aim of this study was to determine the presence and extent of circadian oscillation in the transcriptome of murine calvarial bone. Materials and Methods: Cohorts of 8-week-old male AKR/J mice were maintained in a controlled 12-h light:12-h dark cycle on an ad libitum diet for 2 weeks. Groups of three mice were killed every 4 h over a 48-h period. The level of gene expression at successive times-points was determined by quantitative RT-PCR and Affymetrix microarray. Data were analyzed using multiple statistical time series algorithms, including Cosinor, Fisher g-test, and the permutation time test. Results: Both the positive (Bmal1, Npas2) and negative (Cry1, Cry2, Per1, Per2, Per3) elements of the circadian transcriptional apparatus and their immediate downstream targets and mediators (Dbp, Rev-erb␣, Rev-erb␤) exhibited oscillatory expression profiles. Consistent with findings in other tissues, the positive and negative elements were in antiphase relative to each other. More than 26% of the genes present on the microarray displayed an oscillatory profile in calvarial bone, comparable with the levels observed in brown and white adipose tissues and liver; however, only a subset of 174 oscillating genes were shared among all four tissues. Conclusions: Our findings show that the components of the circadian transcriptional apparatus are represented in calvarial bone and display coordinated oscillatory behavior. However, these are not the only genes to display an oscillatory expression profile, which is seen in multiple pathways involving oxidative phosphorylation and lipid, protein, and carbohydrate metabolism.

Collagen type XI α1 may be involved in the structural plasticity of the vertebral column in Atlantic salmon (Salmo salar L.)

“…However, much of the effect may have been masked by the circadian rhythm of bone tissue, and as is known in mouse bone, 26% of the transcriptome exhibits a circadian pattern (Zvonic et al, 2007). Candidate pathways may therefore have a circadian rhythm; for example, bone formation increases during the night in mammals (Pandi-Perumal et al, 2006), a process that would not have been detected by our sampling regime (sampling was performed during the day).…”

Variations along the 24-hour cycle of circulating osteoprotegerin and soluble RANKL: a rhythmometric analysis

“…Putative synchronizing hormones include parathyroid hormone, melatonin, glucocorticoids and food-dependent peptides, such as glucagon-like peptide 2 [5][6][7][8][9][10][11][12]. Expression of clock genes in osteoblasts has recently been demonstrated, and is consistent with the concept of a bone peripheral clock [13,14].…”

Pharmacological modulators of the circadian clock as potential therapeutic drugs

“…Components of a molecular clock underlying rhythmic gene expression have been characterized in neurons of the suprachiasmatic nucleus (SCN) [23,24], in liver [23][24][25][26][27], heart [26], synchronized fibroblasts [28], adipose tissue [29], adrenal gland [30], skeletal muscle [31], pituitary [32] and pineal [33] glands, calvarial bone [34], as well as in epithelial cells of lung [35,36] and gastrointestinal tract [37][38][39]. In order to ensure proper temporal organization in metabolism and behavior at the level of an organism, the multiple tissue-specific transcriptional oscillations have to be synchronized with the natural 24-hr cycle.…”