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Interrelationship between signal transduction pathways and 1,25(OH)2D3 in UMR106 osteoblastic cells
W Yang1, S J Hyllner, S Christakos
1Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA.
Summary
Signal transduction pathways modulate vitamin D
Area of Science:
- Molecular Endocrinology
- Cell Biology
- Biochemistry
Background:
- 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] is crucial for bone health.
- Osteoblastic cells (UMR106) are key in bone remodeling.
- Understanding vitamin D receptor (VDR) regulation is vital.
Purpose of the Study:
- To investigate how signal transduction pathways interact with 1,25(OH)2D3 action.
- To elucidate the mechanisms of VDR and target gene regulation by cAMP and protein kinase C.
- To determine the role of cellular phosphorylation in vitamin D-mediated gene expression.
Main Methods:
- UMR106 osteoblastic cells were treated with 8-bromo-cAMP and phorbol ester (TPA).
- VDR, 25(OH)D3 24-hydroxylase (24(OH)ase), and osteopontin (OPN) mRNA and gene transcription were analyzed.
- Transfection studies with VDR and OPN promoter constructs were performed.
Main Results:
- cAMP upregulated VDR, enhancing 1,25(OH)2D3 induction of 24(OH)ase and OPN.
- TPA enhanced 1,25(OH)2D3-induced OPN transcription via the OPN promoter, independent of VDR.
- cAMP-mediated potentiation was partly due to VDR upregulation.
Conclusions:
- Signal transduction pathways significantly influence 1,25(OH)2D3-mediated gene expression in osteoblastic cells.
- cAMP enhances 1,25(OH)2D3 action primarily through VDR upregulation.
- Protein kinase C modulates 1,25(OH)2D3 effects on OPN transcription via a distinct promoter mechanism.