Next Article in Journal
Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy
Previous Article in Journal
Effects of Light-Emitting Diode Irradiation on Growth Characteristics and Regulation of Porphyrin Biosynthesis in Rice Seedlings
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(3), 642; doi:10.3390/ijms18030642

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

1
Division of Medical Clinical Oncology, The University of Kansas Medical Center, Kansas City, KS 66160, USA
2
Departments of Internal Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
3
Orthopedic Surgery, The University of Kansas Medical Center, Kansas City, KS 66160, USA
4
Dietetics and Nutrition, The University of Kansas Medical Center, Kansas City, KS 66160, USA
5
Midwest Biomedical Research Foundation-KCVAMC Affiliate, Kansas City, KS 64128, USA
6
Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA
7
Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS 66160, USA
8
Kidney Institute, The University of Kansas Medical Center, Kansas City, KS 66160, USA
9
Sarah Cannon HCA Midwest Health Cancer Network, Overland Park, KS 66209, USA
10
Hematology and Oncology, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA
11
School of Dentistry, University of Missouri-Kansas City, Kansas City, MO 64108, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 3 November 2016 / Revised: 14 February 2017 / Accepted: 15 February 2017 / Published: 16 March 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [12074 KB, uploaded 16 March 2017]   |  

Abstract

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. View Full-Text
Keywords: biomarkers; calcitriol; fibroblast growth factor 23; membrane vesicle biogenesis; microarray; inflammation; osteosarcoma; oxidative stress; Runx2 biomarkers; calcitriol; fibroblast growth factor 23; membrane vesicle biogenesis; microarray; inflammation; osteosarcoma; oxidative stress; Runx2
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Garimella, R.; Tadikonda, P.; Tawfik, O.; Gunewardena, S.; Rowe, P.; Van Veldhuizen, P. Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells. Int. J. Mol. Sci. 2017, 18, 642.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top