miR-221-3p and miR-222-3p downregulation promoted osteogenic differentiation of bone marrow mesenchyme stem cells through IGF-1/ERK pathway under high glucose condition
| Autor: | Juan-fang Zhu, Ning Wang, Kang Gan, Guan-hua Dong |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
MAPK/ERK pathway MAP Kinase Signaling System Endocrinology Diabetes and Metabolism Mesenchyme medicine.medical_treatment Down-Regulation Bone Marrow Cells 030209 endocrinology & metabolism Diabetes Mellitus Experimental 03 medical and health sciences 0302 clinical medicine Endocrinology Downregulation and upregulation Osteogenesis Internal Medicine Animals Medicine Gene silencing 030212 general & internal medicine Osteopontin Insulin-Like Growth Factor I Osteoblasts biology Reverse Transcriptase Polymerase Chain Reaction business.industry Growth factor Cell Differentiation Mesenchymal Stem Cells General Medicine Rats Cell biology MicroRNAs Glucose medicine.anatomical_structure biology.protein Bone marrow Stem cell business |
| Zdroj: | Diabetes Research and Clinical Practice. 167:108121 |
| ISSN: | 0168-8227 |
| DOI: | 10.1016/j.diabres.2020.108121 |
| Popis: | Objective This study aims to investigate the roles of miR-221-3p and miR-222-3p in the regulation of osteogenic differentiation of bone marrow mesenchyme stem cells (BMSCs) under high glucose condition. Materials and methods The expreesions of miR-221-3p, miR-222-3p and insulin-like growth factor 1 (IGF-1) were detected by qRT-PCR. The protein levels of osteoblast-related proteins (Osterix, Runx-2 and Osteopontin) were detected by western blot. Whether miR-221-3p and miR-222-3p can target IGF-1 was assessed by dual luciferase reporter gene assay. Results miR-221-3p and miR-222-3p were up-regulated in the mandibles of diabetic rats and BMSCs cultured in high glucose condition. Silencing miR-221-3p or/ and miR-222-3p increased ALP activity and up-regulated osteoblast-related protein levels, and the simultaneous silence the two miRNAs showed stronger effects on ALP activity and osteoblast-related protein levels. Next, we confirmed that miR-221-3p and miR-222-3p both targeted IGF-1 and cooperatively regulated its expression. Besides, miR-221-3p and miR-222-3p regulated ERK activation through IGF-1. Silencing miR-221-3p and miR-222-3p promoted osteogenic differentiation of BMSCs through IGF-1 under high glucose condition. Conclusion miR-221-3p and miR-222-3p inhibited osteogenic differentiation of BMSCs via IGF-1/ERK pathway under high glucose condition. |
| Databáze: | OpenAIRE |
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