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 ¥á up-regulates the Expression of beta2 Adrenergic Receptor via NF-¥êB-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 (TNF¥á) is a multifunctionalinflammatory cytokine that regulates various cellular and biologicalprocesses. Increased levels of TNF¥á have been implicatedin a number of human diseases including diabetesand arthritis. Sympathetic nervous system stimulation via thebeta2-adrenergic receptor (¥â2AR) in osteoblasts suppressesosteogenic activity. We previously reported that TNF¥á upregulates¥â2AR expression in murine osteoblastic cells andthat this modulation is associated with TNF¥á inhibition ofosteoblast differentiation. In our present study, we exploredwhether TNF¥á induces ¥â2AR expression in human osteoblastsand then identified the downstream signaling pathway.Our results indicated that ¥â2AR expression was increasedin Saos-2 and C2C12 cells by TNF¥á treatment, and thatthis increase was blocked by the inhibition of NF-¥êB activation.Chromatin immunoprecipitation and luciferase reporterassay results indicated that NF-¥êB directly binds to its cognateelements on the ¥â2AR promoter and thereby stimulates¥â2AR expression. These findings suggest that the activationof TNF¥á signaling in osteoblastic cells leads to an upregulationof ¥â2AR and also that TNF¥á induces ¥â2AR expressionin an NF-¥êB-dependent manner.
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KEYWORD
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TNF¥á, ¥â2 adrenergic receptor, NF-¥êB, osteoblast
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