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KMID : 0848120130380030121
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International Journal of Oral Biology
2013 Volume.38 No. 3 p.121 ~ p.126
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Tumor Necrosis Factor α up-regulates the Expression of beta2 Adrenergic Receptor via NF-κB-dependent Pathway in Osteoblasts
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Baek Jeong-Hwa
Baek Kyung-Hwa
Kang Ji-ho
Hwang Hyo-Rin
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Abstract
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Tumor necrosis factor alpha (TNFα) is a multifunctionalinflammatory cytokine that regulates various cellular and biologicalprocesses. Increased levels of TNFα have been implicatedin a number of human diseases including diabetesand arthritis. Sympathetic nervous system stimulation via thebeta2-adrenergic receptor (β2AR) in osteoblasts suppressesosteogenic activity. We previously reported that TNFα upregulatesβ2AR expression in murine osteoblastic cells andthat this modulation is associated with TNFα inhibition ofosteoblast differentiation. In our present study, we exploredwhether TNFα induces β2AR expression in human osteoblastsand then identified the downstream signaling pathway.Our results indicated that β2AR expression was increasedin Saos-2 and C2C12 cells by TNFα treatment, and thatthis increase was blocked by the inhibition of NF-κB activation.Chromatin immunoprecipitation and luciferase reporterassay results indicated that NF-κB directly binds to its cognateelements on the β2AR promoter and thereby stimulatesβ2AR expression. These findings suggest that the activationof TNFα signaling in osteoblastic cells leads to an upregulationof β2AR and also that TNFα induces β2AR expressionin an NF-κB-dependent manner.
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KEYWORD
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TNFα, β2 adrenergic receptor, NF-κB, osteoblast
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