Effects of beta-adrenergic agonists on bone-resorbing activity in human osteoclast-like cells.
In the present study, we demonstrate for the first time that beta-adrenergic agonists stimulate bone-resorbing 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 microM; alpha,beta-adrenergic agonist) up-regulated expression of Int alphaV, CA-II and Cathe K in the osteoclast-like MNCs. Osteoclastic resorbing activity was markedly increased by isoprenaline (1 microM; beta-adrenergic agonist), moderately by epinephrine, but poorly by phenylephrine (1 microM; alpha1-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 beta-adrenergic agonists directly stimulate bone-resorbing activity in matured osteoclasts.
Arai
Michitsugu
M
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
Nagasawa
Tsuneyasu
T
Koshihara
Yasuko
Y
Yamamoto
Seizo
S
Togari
Akifumi
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D001862:Bone Resorption / Q000139:chemically induced*; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011941:Receptors, Adrenergic / Q000235:genetics
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D010656:Phenylephrine; D007545:Isoproterenol; D004837:Epinephrine