RRC ID 51592
Author Tanaka K, Hirai T, Kodama D, Kondo H, Hamamura K, Togari A.
Title α1B -Adrenoceptor signalling regulates bone formation through the up-regulation of CCAAT/enhancer-binding protein δ expression in osteoblasts.
Journal Br J Pharmacol
Abstract BACKGROUND AND PURPOSE:The sympathetic nervous system regulates bone remodelling, in part, through ß2 -adrenoceptor signalling. However, the physiological role of α1 -adrenoceptor signalling in bone in vivo remains unclear. Therefore, to obtain a deeper understanding of bone remodelling by the sympathetic nervous system, we investigated the role of α1B -adrenoceptor signalling in bone metabolism.
EXPERIMENTAL APPROACH:Prazosin, a nonspecific α1 -adrenoceptor antagonist, was administered for 2 weeks in C57BL6 mice, and efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of bone formation by fluorescent labelling of bone. We also compared the bone phenotype of α1B -adrenoceptor null mice (α1B (-/-) ) with that of wild-type littermates.
KEY RESULTS:We demonstrated that the systemic administration of prazosin decreased bone formation. In addition, α1B -adrenoceptor-deficient mice had a lower bone mass due to decreased bone formation but did not exhibit any changes in bone-resorbing activity. Furthermore, stimulation with phenylephrine, a non-specific α1 -adrenoceptor agonist, increased the expression of the transcriptional factor CCAAT/enhancer-binding protein δ (Cebpd) in MC3T3-E1 osteoblastic cells. The overexpression of Cebpd induced cellular proliferation in MC3T3-E1 cells, whereas the silencing of Cebpd suppressed it.
CONCLUSIONS AND IMPLICATIONS:Taken together, these results suggested that α1B -adrenoceptor signalling is required for bone formation and regulated cellular proliferation through a mechanism relevant to the up-regulation of Cebpd in osteoblasts and, thus, provide new evidence for the physiological importance of α1B -adrenoceptor signalling in bone homeostasis.
Volume 173(6)
Pages 1058-69
Published 2016-3
DOI 10.1111/bph.13418
PMID 26750808
PMC PMC5341235
MeSH Adrenergic alpha-1 Receptor Agonists / pharmacology Adrenergic alpha-1 Receptor Antagonists / pharmacology Animals CCAAT-Enhancer-Binding Protein-delta / genetics* Cell Line Femur / metabolism Male Mice, Inbred C57BL Mice, Knockout Osteoblasts / metabolism* Osteogenesis / physiology* Phenylephrine / pharmacology Prazosin / pharmacology Receptors, Adrenergic, alpha-1 / genetics Receptors, Adrenergic, alpha-1 / metabolism* Signal Transduction Up-Regulation
IF 6.583
Times Cited 17
Human and Animal Cells MC3T3-E1(RCB1126)