RRC ID 45159
Author Hirai T, Tanaka K, Togari A.
Title β-adrenergic receptor signaling regulates Ptgs2 by driving circadian gene expression in osteoblasts.
Journal J Cell Sci
Abstract The sympathetic nervous system modulates bone remodeling and mediates the expression of core clock genes in part through the β-adrenergic receptor (β-AR) in osteoblasts. In this study, we show that in MC3T3-E1 osteoblastic cells that isoproterenol (Iso), a non-selective β-AR agonist, upregulated the transcriptional factor Nfil3, and induced rhythmic mRNA expression of prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as Cox2). The rhythmic effects of Iso on Ptgs2 expression were mediated by interplay between the Per2 and Bmal1 clock genes in osteoblasts. In addition, Ptgs2 was significantly decreased in bone after continuous Iso treatment. Overexpression of Nfil3 decreased Ptgs2 expression in MC3T3-E1 cells. Knockdown of Nfil3 upregulated the expression of Ptgs2 in MC3TC-E1 cells, indicating that Nfil3 negatively regulated Ptgs2 in osteoblasts. Furthermore, Iso acutely induced the expression Nfil3 and increased the binding of Nfil3 to the Ptgs2 promoter in MC3T3-E1 cells. These results suggest that Iso-mediated induction of Nfil3 in osteoblasts regulates the expression of Ptgs2 by driving the expression of circadian clock genes. These findings provide new evidence for a physiological role of circadian clockwork in bone metabolism.
Volume 127(Pt 17)
Pages 3711-9
Published 2014-9-1
DOI 10.1242/jcs.148148
PII jcs.148148
PMID 24994935
MeSH Animals Basic-Leucine Zipper Transcription Factors / genetics Basic-Leucine Zipper Transcription Factors / metabolism* CLOCK Proteins / metabolism* Circadian Clocks / genetics Circadian Clocks / physiology Cyclooxygenase 2 / genetics Cyclooxygenase 2 / metabolism* Gene Expression / genetics Male Mice, Inbred C57BL Osteoblasts / metabolism* RNA, Messenger / metabolism Receptors, Adrenergic, beta / genetics Receptors, Adrenergic, beta / metabolism* Signal Transduction* / physiology Transcription Factors / genetics
IF 4.573
Times Cited 19
Human and Animal Cells MC3T3-E1(RCB1126)