PMID- 32194220 OWN - NLM STAT- MEDLINE DCOM- 20201028 LR - 20201028 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 167 DP - 2020 Sep TI - 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. PG - 108121 LID - S0168-8227(20)30371-5 [pii] LID - 10.1016/j.diabres.2020.108121 [doi] AB - 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. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Gan, Kang AU - Gan K AD - Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. FAU - Dong, Guan-Hua AU - Dong GH AD - Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. FAU - Wang, Ning AU - Wang N AD - Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. FAU - Zhu, Juan-Fang AU - Zhu JF AD - Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. Electronic address: zdzhujf@163.com. LA - eng PT - Journal Article DEP - 20200316 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (MicroRNAs) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Bone Marrow Cells/metabolism MH - Cell Differentiation/*genetics MH - Diabetes Mellitus, Experimental/metabolism MH - Down-Regulation/genetics MH - Glucose/genetics/*metabolism MH - Insulin-Like Growth Factor I/*genetics/metabolism MH - MAP Kinase Signaling System/genetics MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - MicroRNAs/*genetics/metabolism MH - Osteoblasts/metabolism MH - Osteogenesis/*genetics MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction OTO - NOTNLM OT - Bone marrow mesenchyme stem cells OT - IGF-1 OT - Osteogenic differentiation OT - miR-221-3p OT - miR-222-3p COIS- Declaration of Competing Interest The authors declared that there is no conflict of interest. EDAT- 2020/03/21 06:00 MHDA- 2020/10/29 06:00 CRDT- 2020/03/21 06:00 PHST- 2019/11/21 00:00 [received] PHST- 2020/02/28 00:00 [revised] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/03/21 06:00 [pubmed] PHST- 2020/10/29 06:00 [medline] PHST- 2020/03/21 06:00 [entrez] AID - S0168-8227(20)30371-5 [pii] AID - 10.1016/j.diabres.2020.108121 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2020 Sep;167:108121. doi: 10.1016/j.diabres.2020.108121. Epub 2020 Mar 16.