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

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. (C) 2020 Elsevier B.V. All rights reserved.