Epigenetic mechanisms are behind the regulation of the key genes associated with the osteoblastic differentiation of the mesenchymal stem cells: The role of zoledronic acid on tuning the epigenetic changes

Epigenetic mechanisms are behind the regulation of the key genes associated with the osteoblastic differentiation of the mesenchymal stem cells: The role of zoledronic acid on tuning the epigenetic changes


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دانشگاه علوم پزشکی تبریز
دانشگاه علوم پزشکی تبریز

نویسندگان: مجید فرش دوستی حق , مهناز غائبی , محمد رضا علی پرستی خاصلویی , صادق سالاری نسب , رضا موسوی اردهائی , قاسم واحدی , سعید سلالی , علی حسن زاده یخفروزان , فاروق معروفی

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نشریه: 19614 , 9 , 234 , 2019

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نویسنده ثبت کننده مقاله مجید فرش دوستی حق
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز تحقیقات کاربردی دارویی
کد مقاله 68330
عنوان فارسی مقاله Epigenetic mechanisms are behind the regulation of the key genes associated with the osteoblastic differentiation of the mesenchymal stem cells: The role of zoledronic acid on tuning the epigenetic changes
عنوان لاتین مقاله Epigenetic mechanisms are behind the regulation of the key genes associated with the osteoblastic differentiation of the mesenchymal stem cells: The role of zoledronic acid on tuning the epigenetic changes
ناشر 9
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ بلی
عنوان نشریه (خارج از لیست فوق)
نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت

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Abstract Mesenchymal stem cells (MSCs) are multipotent stem cells and show distinct features such as capability for self‐renewal and differentiation into several lineages of cells including osteoblasts, chondrocytes, and adipocytes. In this study, the methylation status of the promoter region of zinc finger and BTB domain containing 16 (ZBTB16), twist‐related protein 1(Twist1), de novo DNA methyltransferases 3A (DNMT3A), SRY‐box 9 (Sox9), osteocalcin (OCN), and peroxisome proliferator‐activated receptor γ2 (PPARγ2) genes and their messenger RNA (mRNA) expression levels were evaluated during the osteoblastic differentiation of MSCs (ODMSCs). We planned two experimental groups including zoledronic acid (ZA)‐treated and nontreated cells (negative control) which both were differentiated into the osteoblasts. Methylation level of DNA in the promoter regions was assayed by methylation‐specificquantitative polymerase chain reaction (MS‐qPCR), and mRNA levels of the target inhibitory/stimulatory genes during osteoblastic differentiation of MSCs were measured using real‐time PCR. During the experimental induction of ODMSCs, the mRNA expression of the OCN gene was upregulated and methylation level of its promoter region was decreased. Moreover, Sox9 and PPARγ2 mRNA levels were attenuated and their promoter regions methylation levels were significantly augmented. However, the mRNA expression of the DNMT3A was not affected during the ODMSCs though its methylation rate was increased. In addition, ZA could enhance the expression of the ZBTB16 and decrease its promoter regions methylation and on the opposite side, it diminished mRNA expression of Sox9, Twist1, and PPARγ2 genes and increased their methylation rates. Intriguingly, ZA did not show a significant impact on gene expression and methylation levels the OCN and DNMT3A. We found that methylation of the promoter regions of Sox9, OCN, and PPARγ2 genes might be one of the main mechanisms adjusting the genes expression during the ODMSCs. Furthermore, we noticed that ZA can accelerate the MSCs differentiation to the osteoblast cells via two regulatory processes; suppression of osteoblastic differentiation inhibitor genes including Sox9, Twist1, and PPARγ2, and through promotion of the ZBTB16 expression.

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نویسنده نفر چندم مقاله
مجید فرش دوستی حقنهم
مهناز غائبیهشتم
محمد رضا علی پرستی خاصلوییهفتم
صادق سالاری نسبششم
رضا موسوی اردهائیپنجم
قاسم واحدیچهارم
سعید سلالیسوم
علی حسن زاده یخفروزاندوم
فاروق معروفیاول

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