Effects of β-adrenergic agonists on bone-resorbing activity in human osteoclast-like cells

Abstract

In the present study, we demonstrate for the first time that β-adrenergic agonists stimulate bone-resorbing activity in human osteoclast-like multinucleated cells (MNCs). Osteoclast-like MNCs constitutively expressed mRNA for α1B-, α2B- and β2-adrenergic receptor (AR) in addition to characteristic markers of mature osteoclast, such as calcitonin receptor (CT-R), tartrate-resistant acid phosphatase (TRAP), αV-chain of integrin (Int αV), carbonic anhydrase II (CA-II) and cathepsin K (Cathe K). Epinephrine (1 μM; α,β-adrenergic agonist) up-regulated expression of Int αV, CA-II and Cathe K in the osteoclast-like MNCs. Osteoclastic resorbing activity was markedly increased by isoprenaline (1 μM; β-adrenergic agonist), moderately by epinephrine, but poorly by phenylephrine (1 μM; α1-adrenergic agonist). The actin ring, which was suggested to be correlated with bone-resorbing activity, was clearly observed in osteoclast-like MNCs treated with isoprenaline and epinephrine, but faintly in those treated with phenylephrine. These findings suggest that β-adrenergic agonists directly stimulate bone-resorbing activity in matured osteoclasts.