Tumor Necrosis Factor ${\alpha}$ up-regulates the Expression of beta2 Adrenergic Receptor via NF-${\kappa}B$-dependent Pathway in Osteoblasts

• Published in: International journal of oral biology Vol. 38; no. 3; pp. 121 - 126
• Main Authors: Baek, Kyunghwa, Kang, Jiho, Hwang, Hyo Rin, Baek, Jeong-Hwa
• Format: Journal Article
• Language: Korean
• Published: 2013
• Subjects: {\beta}2$ adrenergic receptor; TNF{\alpha}; osteoblast; NF- ${\kappa}B
• ISSN: 1226-7155

Tumor necrosis factor alpha ($TNF{\alpha}$) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of $TNF{\alpha}$ have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (${\beta}2AR$) in osteoblasts suppresses osteogenic activity. We previously reported that $TNF{\alpha}$ upregulates ${\beta}2AR$ expression in murine osteoblastic cells and that this modulation is associated with $TNF{\alpha}$ inhibition of osteoblast differentiation. In our present study, we explored whether $TNF{\alpha}$ induces ${\beta}2AR$ expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that ${\beta}2AR$ expression was increased in Saos-2 and C2C12 cells by $TNF{\alpha}$ treatment, and that this increase was blocked by the inhibition of NF-${\kappa}B$ activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-${\kappa}B$ directly binds to its cognate elements on the ${\beta}2AR$ promoter and thereby stimulates ${\beta}2AR$ expression. These findings suggest that the activation of $TNF{\alpha}$ signaling in osteoblastic cells leads to an upregulation of ${\beta}2AR$ and also that $TNF{\alpha}$ induces ${\beta}2AR$ expression in an NF-${\kappa}B$-dependent manner.