Changes in the mRNA expression of osteoblast-related genes in response to β3-adrenergic agonist in UMR106 cells

Abstract

Activation of adrenergic receptors (AR) was demonstrated to result in either bone gain or bone loss depending on the activated AR subtypes and concentrations of agonists used. While β2-AR agonist was extensively investigated as an osteopenic agent, effects of β3-AR activation on osteoblasts were still elusive. Rat osteoblast-like UMR106 cells were herein found to express several AR subtypes, including β3-AR. After exposure to a low-dose β3-AR agonist BRL37344 (10 nmol L-1), UMR106 cells downregulated the mRNA expression of transcription factors Runx2 and Dlx5, which are important for initiation of osteoblast differentiation. Low-dose BRL37344 also decreased the expression ratio of receptor activator of nuclear factor kB ligand (RANKL) over osteoprotegerin (OPG), suggesting the protective effect of β3-AR agonist against bone resorption. Alkaline phosphatase expression was markedly decreased, whereas expressions of osteocalcin and osteopontin were increased by 100 nmol L-1 BRL37344, indicating that β3-AR activation could accelerate the transition of matrix maturation stage to mineralization stage. In conclusion, b3-AR activation in rat osteoblasts induced alteration in the expression of osteoblast-related transcription factor genes as well as genes required for bone formation and resorption. The present results also suggest that, besides β2-AR, β3-AR is another AR subtype responsible for the sympathetic nervous system-induced bone remodeling. Copyright © 2009 John Wiley & Sons, Ltd.