Effective role of Curcumin on expression regulation of EZH2 histone methyltransferase as a dynamic epigenetic factor in osteogenic differentiation of human mesenchymal stem cells |
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| Institution: | 1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;3. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;4. Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;5. Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;6. Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran;1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Guangzhou, PR China;2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, PR China;1. University of Puerto Rico Río Piedras, San Juan, Puerto Rico;2. University of Puerto Rico Cayey, Cayey, Puerto Rico;1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran;3. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran |
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| Abstract: | BackgroundEfficient differentiation of mesenchymal stem cells (MSCs) into a desired cell lineage remains challenging in cell-based therapy and regenerative medicine. Numerous efforts have been made to efficiently promote differentiation of MSCs into osteoblast lineage. Accordingly, epigenetic signatures emerge as a key conductor of cell differentiation. Among them, Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase appears to suppress osteogenesis. Curcumin is an osteoinductive natural polyphenol compound which supposedly modulates epigenetic mechanisms. Hence, the current study aims to address the role of the EZH2 epigenetic factor in osteogenic activity of MSCs after Curcumin treatment.MethodsThe effect of Curcumin on viability and osteogenic differentiation was evaluated at different time points in vitro. The expression level of EZH2 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) after 14 and 21 days.ResultsMTT results showed no cytotoxic effects at concentrations of 10 and 15 μM of Curcumin and cells survived up to 70 % at all time-points. qRT-PCR results demonstrated that Curcumin significantly enhanced the expression levels of osteogenic markers that included Runx2, Osterix, Collagen type I, Osteopontin and Osteocalcin at day 21.ConclusionsInterestingly, we observed that the expression level of the EZH2 gene was downregulated in the presence of Curcumin compared to the control group during osteogenesis. This study confirmed that Curcumin acts as an epigenetic switch to regulate osteoblast differentiation specifically through the EZH2 suppression. |
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