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.

Abstract:

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.

authors

Gan K,Dong GH,Wang N,Zhu JF

doi

10.1016/j.diabres.2020.108121

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

108121

eissn

0168-8227

issn

1872-8227

pii

S0168-8227(20)30371-5

journal_volume

167

pub_type

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