کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1985070 1539982 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bone morphogenetic protein receptors and bone morphogenetic protein signaling are controlled by tumor necrosis factor-α in human bone cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Bone morphogenetic protein receptors and bone morphogenetic protein signaling are controlled by tumor necrosis factor-α in human bone cells
چکیده انگلیسی

Bone morphogenetic proteins (BMP) stimulate osteoblast differentiation by signal transduction via three BMP receptors (BMPR-IA, -IB and -II), whereas the inflammatory cytokine tumor necrosis factor-α (TNF-α) has been shown to suppress osteoblast differentiation. Although the mechanisms which regulate the BMPR are not yet known, it is possible that they may be negatively controlled by TNF-α, thereby inhibiting BMP-induced osteoblast differentiation. To test this hypothesis, we have examined the effects of TNF-α on BMPR-IA, -IB and -II expression and the functional consequences of this cytokine on BMPR-mediated functions in human bone cells. The results showed that although TNF-α down-regulated BMPR-IA and -II transcripts, it increased the level of BMPR-IB mRNA via a MAPK-dependent pathway. In marked contrast, however, TNF-α nevertheless caused marked down-regulation of the expression of the BMPR-IB surface antigen specifically. Moreover, the cytokine-induced decrease in BMPR-IB expression was found to be associated with the concurrent presence of a ‘soluble’ form of this antigen in supernatants of TNF-α-treated cultures. Furthermore, the TNF-α-induced loss of BMPR-IB was found to ablate BMP-2-stimulated bone cell functions, including phosphorylation of Smad1/5/8, alkaline phosphatase activity and osteocalcin expression. In conclusion, our study has provided evidence, for the first time, that BMPR can be differentially modulated by TNF-α at both the post-transcriptional and post-translational levels, with the TNF-α-induced shedding of the BMPR-IB antigen associated with a significantly diminished response to BMP-2 in vitro.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 38, Issue 10, 2006, Pages 1794–1807
نویسندگان
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