International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Tumor Necrosis Factor ${\alpha}$ up-regulates the Expression of beta2 Adrenergic Receptor via NF-${\kappa}B$-dependent Pathway in Osteoblasts

  • Baek, Kyunghwa (Department of Pharmacology, College of Dentistry, Research Institute of Oral Biology, Gangneung-Wonju National University) ;
  • Kang, Jiho (Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Hwang, Hyo Rin (Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Baek, Jeong-Hwa (Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University)
  • Received : 2013.07.16
  • Accepted : 2013.08.07
  • Published : 2013.09.30
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Abstract

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.

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References

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