Novel Mechanism of Negative Regulation of 1,25-Dihydroxyvitamin D3-induced 25-Hydroxyvitamin D3 24-Hydroxylase (Cyp24a1) Transcription

Seth-Vollenweider, Tanya; Joshi, Sneha; Dhawan, Puneet; Sif, Saı̈d; Christakos, Sylvia

doi:10.1074/jbc.m114.583302

Cited by 36 publications

(26 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, there appears to be a direct negative feedback loop between interferon signaling and expression of extracellular matrix genes by osteoblasts. Interestingly, PRMT5 has been shown to repress 1, 25-dihydroxy vitamin D3 (1,25(OH) 2 D 3 ) catabolism by negatively regulating Cyp24a1, a 25-hydroxyvitamin D3 24-hydroxylase [37]. Upon PRMT5 inhibition, levels of Cyp39a1, 24 S- hydroxycholesterol 7-alpha-hydroxylase, an enzyme involved in Vitamin D precursor metabolism were increased (0.9 fold, log2FC).…”

Section: Resultsmentioning

confidence: 99%

PRMT5 inhibition promotes osteogenic differentiation of mesenchymal stromal cells and represses basal interferon stimulated gene expression

Kota

Roening

Patel

et al. 2018

Bone

View full text Add to dashboard Cite

Protein arginine methyltransferases (PRMTs) catalyze symmetric and asymmetric methylation on arginine residues of multiple protein targets including histones and have essential roles in organismal development and disease. PRMT5 mediates symmetric di-methylation (sDMA) of arginine 2 (H3R2me2s) and arginine 8 on histone 3 (H3R8me2s), arginine 3 on histones 2A and 4 (H2A/H4R3me2s) as well as several non-histone substrates like Sm proteins. Here, we found that selective inhibition of PRMT5 in mesenchymal stromal cells (MSCs) led to a reduction in colony forming units (CFUs) and increased osteoblast differentiation. PRMT5 inhibition blocked global symmetric dimethylation of H3R8 and H4R3 but not on H3R2. Genome-wide expression analysis by total RNA sequencing of mesenchymal stromal cells undergoing osteogenic differentiation revealed significant reduction in the intrinsic expression of several interferon-stimulated genes (ISGs) upon PRMT5 inhibition. Effects of PRMT5 inhibition on basal ISG expression and osteogenic differentiation was effectively blocked by exogenous activation of type I IFN signaling. Together, these results indicate important functions for PRMT5 in the regulation of basal interferon gene expression in MSCs and in the control of differentiation potential of MSCs during osteogenic differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

PRMT5 inhibition promotes osteogenic differentiation of mesenchymal stromal cells and represses basal interferon stimulated gene expression

Kota

Roening

Patel

et al. 2018

Bone

View full text Add to dashboard Cite

show abstract

“…Most of the genes constituting this panel serve as biomarkers for efficacy, prognosis, diagnosis, disease progression (targeting inflammation, oxidative stress and vesiculation gene networks) and response to therapy [43,44,45,46,47,48,49,50,51,52,53,54,55,56,57]. Vitamin D mediated genetic networks such as those identified in our study, for example inflammation, oxidative stress and membrane vesicle biogenesis pathways in 143B cells, shed insight into the mechanism(s) underlying antineoplastic effects of vitamin D in human OS.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

Garimella

Tadikonda

Tawfik

et al. 2017

IJMS

View full text Add to dashboard Cite

Osteosarcoma (OS) is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a) inflammation and immunity; (b) formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium), quantity of gap junctions and skeletogenesis; (c) bone mineral density; and (d) cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles. Ingenuity pathway analysis revealed significant reduction in Runx2 target genes such as fibroblast growth factor -1, -12 (FGF1 and FGF12), bone morphogenetic factor-1 (BMP1), SWI/SNF related, matrix associated actin dependent regulator of chromatin subfamily a, member 4 (SMARCA4), Matrix extracellular phosphoglycoprotein (MEPE), Integrin, β4 (ITGBP4), Matrix Metalloproteinase -1, -28 (MMP1 and MMP28), and signal transducer and activator of transcription-4 (STAT4) in vitamin D treated 143B OS cells. These genes interact with the inflammation, oxidative stress and membrane vesicle biogenesis gene networks. Vitamin D not only inhibited the expression of Runx2 target genes MMP1, MMP28 and kallikrein related peptidase-7 (KLK7), but also migration and invasion of 143B OS cells. Vitamin D regulated Runx2 target genes or their products represent potential therapeutic targets and laboratory biomarkers for applications in translational oncology.

show abstract

“…On the other hand, recent studies in liver stellate cells suggested that 1,25(OH) 2 D 3 -mediated repression of a profibrotic gene expression program induced by TGFβ does not involve the apparent recruitment of corepressors SMRT and NCoR (162). In addition to SRC1, CBP and MED1, Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF chromatin remodeling complex, has been reported to play a fundamental role in 1,25(OH) 2 D 3 induced transcription (163). C/EBP and BRG1 are components of the same complex and are recruited to the C/EBP site of the CYP24A1 gene by 1,25(OH) 2 D 3 .…”

Section: The Vitamin D Receptor and Genomic Mechanisms Of Actionmentioning

confidence: 99%

Biology and Mechanisms of Action of the Vitamin D Hormone

Pike

Christakos

2017

Endocrinology and Metabolism Clinics of North America

Self Cite

223

184

View full text Add to dashboard Cite

Synopsis The central role of hormonal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is to regulate calcium and phosphorus homeostasis via actions in intestine, kidney and bone. These actions as well as many additional pleiotropic activities in a wide variety of cell types not involved in mineral metabolism are mediated by the vitamin D receptor (VDR), a nuclear protein that functions in virtually all target tissues to regulate the expression of genes and gene networks. Recent studies using genome-wide scale techniques have extended fundamental ideas regarding vitamin D mediated control of gene expression while simultaneously revealing a series of new concepts as well. In this article, we summarize our current view of the biological actions of the vitamin D hormone and then focus on new concepts that drive our understanding of the mechanisms through which vitamin D operates.

show abstract

Novel Mechanism of Negative Regulation of 1,25-Dihydroxyvitamin D3-induced 25-Hydroxyvitamin D3 24-Hydroxylase (Cyp24a1) Transcription

Cited by 36 publications

References 60 publications

PRMT5 inhibition promotes osteogenic differentiation of mesenchymal stromal cells and represses basal interferon stimulated gene expression

PRMT5 inhibition promotes osteogenic differentiation of mesenchymal stromal cells and represses basal interferon stimulated gene expression

Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

Biology and Mechanisms of Action of the Vitamin D Hormone

Contact Info

Product

Resources

About