Long non-coding RNA H19 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by regulating microRNA-140-5p/SATB2 axis

• Published in: Journal of biosciences Vol. 45; no. 1
• Main Authors: Bi, Hu, Wang, Dong, Liu, Xiaoyu, Wang, Gang, Wu, Xuejian
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.12.2020; Springer Nature B.V
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - metabolism; Assaying; Bioinformatics; Biomedical and Life Sciences; Biomedical materials; Biomedicine; Bone growth; Bone marrow; Bone Marrow Cells - metabolism; Bones; Cell Biology; Cell differentiation; Cell Differentiation - genetics; Cells, Cultured; Depletion; Differentiation (biology); Gene expression; Gene Expression Regulation, Developmental - genetics; Homeobox; Humans; Life Sciences; Long bone; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Region Binding Proteins - metabolism; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Microbiology; MicroRNAs; MicroRNAs - metabolism; miRNA; Molecular modelling; Non-coding RNA; Nucleic acids; Osteoblasts - metabolism; Osteogenesis; Osteogenesis - genetics; Phosphatase; Plant Sciences; Ribonucleic acid; RNA; RNA, Long Noncoding - metabolism; Signal Transduction - genetics; Silk; Stem cells; Transcription Factors - genetics; Transcription Factors - metabolism; Zoology; H19; differentiation; osteogenesis; microRNA-140-5p; mesenchymal stem cells; bone marrow
• ISSN: 0250-5991; 0973-7138
• DOI: 10.1007/s12038-020-0024-y

The osteogenic differentiation of mesenchymal stem cells (MSCs) has potential clinical values in the treatment of bone-related diseases. Long non-coding RNA H19 and microRNA-140-5p (miR-140-5p) have attracted much attention of researchers by virtue of their biological importance in cell differentiation and bone formation. Moreover, bioinformatics analyses suggest that miR-140-5p have the potential to bind with H19 and SATB homeobox 2 (SATB2). In this study, we further explored whether H19 could regulate osteogenic differentiation of human bone marrow-derived MSCs (BM-MSCs) by miR-140-5p/SATB2 axis. RT-qPCR assay was conducted to examine the expression of H19, miR-140-5p and SATB2. The osteogenic differentiation capacity of BM-MSCs was assessed through alkaline phosphatase (ALP) activity and osteogenic marker expression. The relationships among H19, miR-140-5p and SATB2 were examined through bioinformatics analyses, luciferase reporter assay, RIP assay and RNA pull-down assay. H19 expression was remarkably increased and miR-140-5p expression was dramatically reduced during osteogenic differentiation of BM-MSCs. Functional analyses revealed that H19 overexpression or miR-140-5p depletion accelerated osteogenic differentiation of BM-MSCs. Conversely, H19 loss or miR-140-5p increase suppressed osteogenic differentiation of BM-MSCs. MiR-140-5p was confirmed as a target of H19, and miR-140-5p could bind to SATB2 as well. Moreover, H19 knockdown reduced SATB2 expression by upregulating miR-140-5p. Additionally, miR-140-5p depletion antagonized the inhibitory effect of H19 knockdown on osteogenic differentiation of BM-MSCs. And, miR-140-5p inhibited osteogenic differentiation of BM-MSCs by targeting SATB2. In conclusion, H19 promoted osteogenic differentiation of BM-MSCs through regulating miR-140-5p/SATB2 axis, deepening our understanding on the molecular mechanisms of H19 in coordinating osteogenesis.