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Biomed Rep. 2018 May;8(5):407-416. doi: 10.3892/br.2018.1075. Epub 2018 Mar 9.

Suppression of osteoclastogenesis via α2-adrenergic receptors.

Author information

1
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi 464-8650, Japan.
2
Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Aichi 464-8650, Japan.
3
Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, IN 46202, USA.
4
Laboratory of Neuropharmacology, School of Pharmacy, Aichi-Gakuin University, Nagoya, Aichi 464-8650, Japan.
5
Laboratory of Medical Resources, School of Pharmacy, Aichi-Gakuin University, Nagoya, Aichi 464-8650, Japan.

Abstract

The sympathetic nervous system is known to regulate osteoclast development. However, the involvement of α2-adrenergic receptors (α2-ARs) in osteoclastogenesis is not well understood. In the present study, their potential role in osteoclastogenesis was investigated. Guanabenz, clonidine and xylazine were used as agonists of α2-ARs, while yohimbine and idazoxan were employed as antagonists. Using RAW264.7 pre-osteoclast and primary bone marrow cells, the mRNA expression of the osteoclast-related genes nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K was evaluated following induction with receptor activator of nuclear factor κB ligand (RANKL). TRAP staining was also conducted to assess effects on osteoclastogenesis in mouse bone marrow cells in vitro. Administration of 5-20 µM guanabenz (P<0.01, for RANKL-only treatment), 20 µM clonidine (P<0.05, for RANKL-only treatment) and 20 µM xylazine (P<0.05, for RANKL-only treatment) attenuated RANKL-induced upregulation of NFATc1, TRAP and cathepsin K mRNA. Furthermore, the reductions in these mRNAs by 10 µM guanabenz and 20 µM clonidine in the presence of RANKL were attenuated by 20 µM yohimbine or idazoxan (P<0.05). The administration of 5-20 µM guanabenz (P<0.01, for RANKL-only treatment) and 10-20 µM clonidine (P<0.05, for RANKL-only treatment) also decreased the number of TRAP-positive multi-nucleated osteoclasts. Collectively, the present study demonstrates that α2-ARs may be involved in the regulation of osteoclastogenesis.

KEYWORDS:

agonist; antagonist; osteoclast; osteoclastogenesis; α2-adrenergic receptors

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