mirna 27a 3p promotes osteogenic differentiation of human mesenchymal stem cells through targeting atf3

• DOI: 10.26355/eurrev_201908_18632
• Publication Date: 2019-08-01
• Authors: X-X Wang; S-S Guo; B-H Zhu; Y-C Fu; S-R Zhao
• Keywords: 0301 basic medicine; 0303 health sciences; Activating Transcription Factor 3; Chemokine CCL27; Down-Regulation; Cell Differentiation; Mesenchymal Stem Cells; 03 medical and health sciences; MicroRNAs; Gene Expression Regulation; Osteogenesis; Case-Control Studies; Humans; Osteoporosis; 3' Untranslated Regions; Cells, Cultured

To elucidate whether miRNA-27a-3p can promote osteogenic differentiation of hMSCs by targeting ATF3, thus alleviating osteoporosis symptoms.The serum levels of miRNA-27a-3p in osteoporosis patients (n=20) and normal controls (n=20) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Human bone marrow mesenchymal stem cells (hMSCs) were subjected to osteogenic differentiation for 1, 3 and 7 days. Subsequently, mRNA levels of miRNA-27a-3p, ALP, and Bglap in hMSCs were determined by qRT-PCR. The regulatory effects of miRNA-27a-3p levels and the mRNA levels of ALP, Bglap, and Runx2 were detected. After the overexpression or knockdown of miRNA-27a-3p, we evaluated the changes in the osteogenic differentiation by alizarin red staining and ALP staining. Through Dual-Luciferase Reporter Gene Assay, we verified the binding relationship between miRNA-27a-3p and ATF3. Rescue experiments were finally conducted to prove whether miRNA-27a-3p regulated the osteogenic differentiation by targeting ATF3.The serum level of miRNA-27a-3p remained lower in osteoporosis patients relative to controls. With the prolongation of osteogenic differentiation, the mRNA levels of miRNA-27a-3p, ALP, and Bglap gradually increased. The overexpression of miRNA-27a-3p upregulated mRNA and the protein levels of osteogenesis-related genes, increased ALP activity, and enhanced mineralization capacity. The knockdown of miRNA-27a-3p obtained the opposite trends. MiRNA-27a-3p could target ATF3, and the overexpression of ATF3 reversed the promotive effects of miRNA-27a-3p on osteogenic differentiation.MiRNA-27a-3p promotes the differentiation of hMSCs into osteoblasts by targeting ATF3, thus alleviating osteoporosis symptoms.