Changes in the mRNA expression of osteoblast‐related genes in response to <i>β</i>₃‐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 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.