کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1992558 1541078 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
1,25-Dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly downstream of the gene's transcriptional start site
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
1,25-Dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly downstream of the gene's transcriptional start site
چکیده انگلیسی

Canonical Wnt signaling is essential for bone formation. Activation involves binding of secreted members of the Wnt family of proteins with a membrane receptor Frizzled on osteoblasts, an interaction that is facilitated by LRP5/LRP6 co-receptors. LRP5 is known to play a particularly important role in bone formation such that the loss of this protein results in a reduction in osteoblast number, a delay in mineralization and a reduction in peak BMD. During the course of a VDR ChIP-chip analysis we found that 1,25(OH)2D3 could induce binding of the VDR to sites within the Lrp5 gene locus. Importantly, this interaction between 1,25(OH)2D3-activated VDR and the Lrp5 gene led to both a modification in chromatin structure within the Lrp5 locus and the induction of LRP5 mRNA transcripts in vivo as well as in vitro. One site within Lrp5 was discovered to confer 1,25(OH)2D3 response to a heterologous promoter in osteoblastic cells, permitting both the identification and characterization of the component VDRE. While the regulatory region in Lrp5 was highly conserved in the human genome, the VDRE was not. Our studies show that 1,25(OH)2D3 can enhance the expression of a critical component of the Wnt signaling pathway which is known to impact osteogenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 103, Issues 3–5, March 2007, Pages 440–445
نویسندگان
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