Dataset Information

?1B -Adrenoceptor signalling regulates bone formation through the up-regulation of CCAAT/enhancer-binding protein ? expression in osteoblasts.

ABSTRACT:

Background and purpose

The sympathetic nervous system regulates bone remodelling, in part, through ß2 -adrenoceptor signalling. However, the physiological role of ?1 -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 ?1B -adrenoceptor signalling in bone metabolism.

Experimental approach

Prazosin, a nonspecific ?1 -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 ?1B -adrenoceptor null mice (?1B (-/-) ) with that of wild-type littermates.

Key results

We demonstrated that the systemic administration of prazosin decreased bone formation. In addition, ?1B -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 ?1 -adrenoceptor agonist, increased the expression of the transcriptional factor CCAAT/enhancer-binding protein ? (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 ?1B -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 ?1B -adrenoceptor signalling in bone homeostasis.

SUBMITTER: Tanaka K

PROVIDER: S-EPMC5341235 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

α1B -Adrenoceptor signalling regulates bone formation through the up-regulation of CCAAT/enhancer-binding protein δ expression in osteoblasts.

Tanaka Kenjiro K Hirai Takao T Kodama Daisuke D Kondo Hisataka H Hamamura Kazunori K Togari Akifumi A

British journal of pharmacology 20160222 6

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Prazosin, a nonspecific α1 -adrenoceptor antagonist, was admini ...[more]

PMID: 26750808

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