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

In the present study, we demonstrate for the first time that beta-adrenergic agonists stimulate bone-resorting activity in human osteoclast-like multinucleated cells (MNCs). Osteoclast-like MNCs constitutively expressed mRNA for alpha1B-, alpha2B- and beta2-adrenergic receptor (AR) in addition to characteristic markers of mature osteoclast, such as calcitonin receptor (CT-R), tartrate-resistant acid phosphatase (TRAP), alphaV-chain of integrin (Int alphaV), carbonic anhydrase II (CA-II) and cathepsin K (Cathe K). Epinephrine (1 muM; alpha,beta-adrenergic agonist) up-regulated expression of Int aV, CA -II and Cathe K in the osteoclast-like MNCs. Osteoclastic resorbing activity was markedly increased by isoprenaline (1 muM; beta-adrenergic agonist), moderately by epinephrine, but poorly by phenylephrine (1 muM; alpha1-adrenergic agonist). The actin ring, which was suggested to be correlated with bone-resorting activity, was clearly observed in osteoclast-like MNCs treated with isoprenaline and epinephrine, but faintly in those treated with phenylephrine. These findings suggest that beta-adrenergic agonists directly stimulate bone-resorting activity in matured osteoclasts. (C) 2003 Elsevier Science B.V. All rights reserved.