Epigenetic regulation of specific transcription factors in osteogenicdifferentiation of mesenchymal stem cells

Abstract

An abundance of experiments have been performed to clarify the differentiation process of mesenchymal stem cells (MSCs). Osteogenic differentiation and in vitro conditions favoring these cell lineages have attracted the attention of many researchers. Moreover, the gene expression profile during MSC differentiation toward its main specialized cells (bone, cartilage, and adipose cells) has been mostly understood. In the last decades another layer of investigation has attempted to clarify the epigenetic mechanisms underlying MSC differentiation into its specialized cells. It has been shown that as MSCs progress through the differentiation process, more nonspecific genes undergo DNA methylation to prevent differentiation into improper cell fates. Moreover, promoters of lineage-specific genes are strongly hypomethylated in MSCs during differentiation. The main objective of this review is to address the role of major epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNAs, especially miRNAs, in osteoblastic differentiation of MSCs and to summarize all the previous studies that have determined the epigenetic alterations of the nuclear genome during osteoblastic differentiation of MSCs.

Regulatory Effect of Resveratrol and Prednisolone on MDR1 Protein Expression in Acute Lymphoblastic Leukemia Cell Line (CCRF-CEM)

“…In our previous research, we demonstrated that resveratrol and prednisolone can reduce the expression of MDR1 gene without changing the methylation pattern of the MDR1 gene . Our observation on these acute lymphoblastic cells CCRF-CEM also showed that resveratrol and prednisolone can increase the apoptosis of these cancer cells by changing the expression of microRNAs miR 15a and miR16-1 and also reducing the expression of BAX gene as well as increasing expression of BCL-2 without changing the pattern of methylation of the promoter of BAX and BCL-2 genes (Azimi et al, 2015;Azimi et al, 2016;Heydarabad et al, 2016;. In the present study, we also found that resveratrol and prednisolone can overcome drug resistance caused by increasing the expression of MDR1 in acute lymphoblastic cell CCRF-CEM via reducing the expression of MDR1 in the protein level.…”

Apoptosis Induced by Prednisolone Occurs without Altering the Promoter Methylation of BAX and BCL-2 Genes in Acute Lymphoblastic Leukemia Cells CCRF-CEM

“…GC induces activation of caspase cascade and induces apoptosis in the cell line of lymphoblastic leukemia by increasing in BAX protein and decreasing the BCL2 protein (Azimi et al, 2015;Ghasemi et al, 2018). We know that the level of methylation of the promoters of most genes is associated with their expression, so that the reduction of methylation or hypomethylation triggers the activation of the genes and the increase of methylation inhibits these genes (Heydarabad et al, 2016;Marofi et al, 2019). On one hand, hypomethylation of the oncogenes and the hypermethylation of tumor suppressor genes (TSGs) can lead to disease and cancer (Garcia-Manero et al, 2002;Hervouet et al, 2013).…”