Long noncoding RNA MALAT1 promotes osterix expression to regulate osteogenic differentiation by targeting miRNA‐143 in human bone marrow‐derived mesenchymal stem cells

Abstract

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is essential for the human bone formation, and emerging evidence shows that long non-coding RNAs (lncRNAs) play important roles in hBMSC osteogenic differentiation. MALAT1 is often regarded as a tumor-related lncRNA, but its function in mesenchymal stem cell differentiation remains to be defined. In this study, we aimed to investigate whether MALAT1 regulates Osterix (Osx) expression by sponging miR-143 to promote hBMSC osteogenic differentiation. Firstly, we found that the expression of MALAT1 was much lower in hBMSCs from osteoporosis patients and miR-143 was contrarily higher. In addition, MALAT1 expression increased, and miR-143 decreased when hBMSCs were treated with osteogenic induction. Then, we used short hairpin RNAs to knockdown MALAT1, and the results showed that hBMSC osteogenic differentiation decreased significantly, indicating that MALAT1 is a positive regulator of osteogenic differentiation in hBMSCs. Furthermore, by luciferase assays, we found that MALAT1 could directly bind to miR-143 and negatively regulate its expression. Similarly, miR-143 could directly bind to the target site on the Osx 3'-UTR and then inhibit Osx expression. Knockdown of MALAT1 decreased Osx expression, and co-transfection of miR-143 inhibitor could rescue Osx mRNA expression. While Osx expression was increased in MALAT1-overexpressing hBMSCs, it was reversed by the miR-143 mimics. Moreover, Osx silencing decreased ALP, OCN, and OPN mRNA expression induced by the miR-143 inhibitor. Altogether, our findings suggest that MALAT1 acts to regulate Osx expression through targeting miR-143; thus, it is considered as a positive regulator in hBMSC osteogenic differentiation.

lncRNA SNHG1 attenuates osteogenic differentiation via the miR‑101/DKK1 axis in bone marrow mesenchymal stem cells

“…it has been reported that lncrnas participate in regulating osteogenic activity. For instance, KcnQ1 opposite strand/antisense transcript 1 (KcnQ1oT1) regulates osteogenic differentiation by sponging microrna (mirna/mir)-214 (5), whereas MalaT1 promotes osterix (oSX) expression to regulate osteogenic differentiation by sponging mirna-143 (6). Small nucleolar rna host gene 1 (SnHG1) is upregulated in numerous types of cancer (7,8), and can attenuate heterogeneous nuclear ribonucleoprotein c-p53 protein interactions to enhance the stability of p53 (4).…”

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

“…Osterix, a specificity protein 1 family (Sp1) of transcription factors, is downstream of Runx2, and is essential for bone formation (Nakashima et al, 2002). For example, lncRNA MALAT1 stimulates osterix expression and osteogenesis of MSCs by sponging miRNA-143 (Gao et al, 2018), and the lncRNA-miRNA pathway is the most classic mechanism of action. In addition, some miRNAs regulate MSCs differentiation through indirect interaction with transcription factors, and lncRNA regulates differentiation of MSCs through others pathways, including Wnt/β-catenin pathway, p38 MAPK pathway, and BMP4 signaling (Ju et al, 2019).…”

MicroRNAs and long noncoding RNAs: new regulators in cell fate determination of mesenchymal stem cells

“…LncRNAs HULC and MALAT1 promote osteoblast differentiation of hBMSCs either by targeting miR-195 or by targeting miRNA-143. 82,83 LncRNA-ANCR inhibits osteogenic differentiation of PDLSCs by targeting miRNA-758, which has a role in promoting Notch2 expression by targeting 3 0 -UTR of Notch2. 84 Other ndings show different functional ways of lncRNAs in regulating osteogenic differentiation of MSCs.…”