Suppression of osteoclastogenesis via α2-adrenergic receptors.

The sympathetic nervous system is known to regulate osteoclast development. However, the involvement of alpha 2-adrenergic receptors (alpha 2-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 alpha 2-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 kappa B ligand (RANKL). TRAP staining was also conducted to assess effects on osteoclastogenesis in mouse bone marrow cells in vitro. Administration of 5-20 mu M guanabenz (P < 0.01, for RANKL-only treatment), 20 mu M clonidine (P < 0.05, for RANKL-only treatment) and 20 mu M 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 mu M guanabenz and 20 mu M clonidine in the presence of RANKL were attenuated by 20 mu M yohimbine or idazoxan (P < 0.05). The administration of 5-20 mu M guanabenz (P < 0.01, for RANKL-only treatment) and 10-20 mu M clonidine (P < 0.05, for RANKL-only treatment) also decreased the number of TRAP-positive multi-nucleated osteoclasts. Collectively, the present study demonstrates that alpha 2-ARs may be involved in the regulation of osteoclastogenesis.