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 beta(2)-AR agonist was extensively investigated as an osteopenic agent, effects of beta(3)-AR activation on osteoblasts were still elusive. Rat osteoblast-like UMR106 cells were herein found to express several AR subtypes, including beta(3)-AR. After exposure to a low-dose beta(3)-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 kappaB ligand (RANKL) over osteoprotegerin (OPG), suggesting the protective effect of beta(3)-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 beta(3)-AR activation could accelerate the transition of matrix maturation stage to mineralization stage. In conclusion, beta(3)-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 beta(2)-AR, beta(3)-AR is another AR subtype responsible for the sympathetic nervous system-induced bone remodeling.
2009 John Wiley & Sons, Ltd.