دورية أكاديمية
ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders.
| العنوان: | ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders. |
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| المؤلفون: | Marofi F; Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Choupani J; Department of Medical Genetic, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, Solali S; Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Vahedi G; Department of Immunology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran, Hassanzadeh A; Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Gharibi T; Department of Immunology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Hagh MF; Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran |
| المصدر: | Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2020; Vol. 20 (18), pp. 2274-2284. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: Netherlands NLM ID: 101265649 Publication Model: Print Cited Medium: Internet ISSN: 1875-5992 (Electronic) Linking ISSN: 18715206 NLM ISO Abbreviation: Anticancer Agents Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Bentham Science Publishers Original Publication: Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, [2006]- |
| مواضيع طبية MeSH: | Bone Diseases/*drug therapy , Transcription Factors/*antagonists & inhibitors , Zoledronic Acid/*pharmacology, Bone Diseases/pathology ; Cell Differentiation/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Mesenchymal Stem Cells/drug effects ; Molecular Structure ; Osteogenesis/drug effects ; RNA, Messenger/antagonists & inhibitors ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Structure-Activity Relationship ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Zoledronic Acid/chemical synthesis ; Zoledronic Acid/chemistry |
| مستخلص: | Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real-time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| معلومات مُعتمدة: | 96.6 Tabriz University of Medical Sciences |
| فهرسة مساهمة: | Keywords: DNA methylation; MS-qPCR; bone disorders; mesenchymal stem cells; osteoblastic differentiation; zoledronic acid |
| المشرفين على المادة: | 0 (RNA, Messenger) 0 (Transcription Factors) 6XC1PAD3KF (Zoledronic Acid) |
| تواريخ الأحداث: | Date Created: 20200724 Date Completed: 20210607 Latest Revision: 20210623 |
| رمز التحديث: | 20231215 |
| DOI: | 10.2174/1871520620666200721101904 |
| PMID: | 32698734 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-5992 |
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| DOI: | 10.2174/1871520620666200721101904 |