Tumor necrosis factor alpha ($TNF{alpha}$) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that ${eta}2$ adrenergic receptor (${eta}2AR$) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether $TNF{alpha}$ modulates ${eta}AR$ expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by $TNF{alpha}$. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of ${eta}AR$, ${eta}2$ and ${eta}3AR$ were found in our analysis to be upregulated by $TNF{alpha}$. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in $TNF{alpha}$-primed C2C12 cells, indicating that $TNF{alpha}$ enhances ${eta}2AR$ signaling in osteoblasts. $TNF{alpha}$ was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a ${eta}2AR$ antagonist, attenuated this $TNF{alpha}$ suppression of osteogenic differentiation. $TNF{alpha}$ increased the expression of receptor activator of NF-${kappa}B$ ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that $TNF{alpha}$ increases ${eta}2AR$ expression in osteoblasts and that a blockade of ${eta}2AR$ attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by $TNF{alpha}$. These findings imply that a crosstalk between $TNF{alpha}$ and ${eta}2AR$ signaling pathways might occur in osteoblasts to modulate their function.