Int J Oral Biol.  2013 Sep;38(3):121-126.

Tumor Necrosis Factor alpha up-regulates the Expression of beta2 Adrenergic Receptor via NF-kappaB-dependent Pathway in Osteoblasts

• Baek K
• Kang J
• Hwang HR
• Baek JH

Abstract

Tumor necrosis factor alpha (TNFalpha) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of TNFalpha have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (beta2AR) in osteoblasts suppresses osteogenic activity. We previously reported that TNFalpha up-regulates beta2AR expression in murine osteoblastic cells and that this modulation is associated with TNFalpha inhibition of osteoblast differentiation. In our present study, we explored whether TNFalpha induces beta2AR expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that beta2AR expression was increased in Saos-2 and C2C12 cells by TNFalpha treatment, and that this increase was blocked by the inhibition of NF-kappaB activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-kappaB directly binds to its cognate elements on the beta2AR promoter and thereby stimulates beta2AR expression. These findings suggest that the activation of TNFalpha signaling in osteoblastic cells leads to an upregulation of beta2AR and also that TNFalpha induces beta2AR expression in an NF-kappaB-dependent manner.

Keyword

TNFalpha; beta2 adrenergic receptor; NF-kappaB; osteoblast

MeSH Terms

Arthritis
Biological Processes
Chromatin Immunoprecipitation
Durapatite
Humans
Luciferases
NF-kappa B
Osteoblasts
Receptors, Adrenergic
Sympathetic Nervous System
Tumor Necrosis Factor-alpha
Up-Regulation
Durapatite
Luciferases
NF-kappa B
Receptors, Adrenergic
Tumor Necrosis Factor-alpha