Modulation of miRNAs by Vitamin C in Human Bone Marrow Stromal Cells.

Ravindra Kolhe,Sadanand Fulzele,Monte Hunter,Carlos Isales,Mark Hamrick,Ashis Mondal,Sudharsan Periyasamy-Thandavan,William Hill,Bharati Mendhe,Chetan Pundkar

doi:10.3390/nu10020186

Abstract

MicroRNAs (miRNAs) are small (18–25 nucleotides), noncoding RNAs that have been identified as potential regulators of bone marrow stromal cell (BMSC) proliferation, differentiation, and musculoskeletal development. Vitamin C is known to play a vital role in such types of biological processes through various different mechanisms by altering mRNA expression. We hypothesized that vitamin C mediates these biological processes partially through miRNA regulation. We performed global miRNA expression analysis on human BMSCs following vitamin C treatment using microarrays containing human precursor and mature miRNA probes. Bioinformatics analyses were performed on differentially expressed miRNAs to identify novel target genes and signaling pathways. Our bioinformatics analysis suggested that the miRNAs may regulate multiple stem cell-specific signaling pathways such as cell adhesion molecules (CAMs), fatty acid biosynthesis and hormone signaling pathways. Furthermore, our analysis predicted novel stem cell proliferation and differentiation gene targets. The findings of the present study demonstrate that vitamin C can have positive effects on BMSCs in part by regulating miRNA expression.

Highlights

Adult stem cell differentiation is a complex process that is heavily influenced by tissue origin and interaction with the cellular microenvironment [1]
With were osteogenic for 3 weeks followed by Alizarin red assay properties, cells were treated with osteogenic media for 3 weeks followed by Alizarin red assay staining and real time polymerase chain reaction (PCR)
We found that these miRNAs target a number of genes that are important for regulating stem cell differentiation, with regard to lineage commitment in musculoskeletal tissues (See Table 4)

Summary

Introduction

Adult stem cell differentiation is a complex process that is heavily influenced by tissue origin and interaction with the cellular microenvironment [1]. Bone marrow stromal cells (BMSCs) are mesenchymal lineage cells that can differentiate into a number of different cell types including osteoblasts, osteocytes, adipocytes, and chondrocytes [2,3]. Micronutrients, including vitamin C, are important factors in musculoskeletal development and BMSC biology [4,5,6,7,8,9,10,11,12,13,14,15]. Vitamin C is a key player in collagen synthesis, cell proliferation, and BMSC differentiation [9,10,11,12,13,14,15]. Vitamin C is an essential nutrient that is not synthesized by most

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Conclusion