Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients

Abstract

Periodontitis impairs the osteogenic differentiation of human periodontal mesenchymal stem cells (hPDLSCs), but the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to have significant roles under both physiologic and pathological conditions. In this study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified a novel lncRNA, osteogenesis impairment-related lncRNA of PDLSCs from periodontitis patients (lncRNA-POIR), the expression of which was significantly decreased in PDLSCs from periodontitis patients (pPDLSCs) and was upregulated by osteogenic induction. To study the functions of lncRNA-POIR, we prepared cells with overexpression and knockdown of lncRNA-POIR and found that lncRNA-POIR positively regulated osteogenic differentiation of hPDLSCs and pPDLSCs both in vitro and in vivo. Using quantitative real-time PCRs (qPCRs) and luciferase reporter assays, we demonstrated that lncRNA-POIR may act as a competing endogenous RNA (ceRNA) for miR-182, leading to derepression of its target gene, FoxO1. In this process, lncRNA-POIR and miR-182 suppress each other and form a network to regulate FoxO1. FoxO1 increased bone formation of pPDLSCs by competing with TCF-4 for β-catenin and inhibiting the canonical Wnt pathway. Finally, inflammation increases miR-182 expression through the nuclear factor-κB pathway, and the miR-182 overexpression in the inflammatory microenvironment resulted in an imbalance in the lncRNA-POIR-miR-182 regulatory network. In conclusion, our results provide novel evidence that this lncRNA-miRNA (microRNA) regulatory network has a significant role in osteogenic differentiation of pPDLSCs and that it has potential as a therapeutic target in mesenchymal stem cells during inflammation.

LncRNA‐PVT1 promotes pancreatic cancer cells proliferation and migration through acting as a molecular sponge to regulate miR‐448

“…Recently, accumulating lncRNAs have been demonstrated as endogenous ceRNAs for specific miRNAs and regulate their function; for instance, in 2016, Lv et al () revealed that lncRNA Unigene56159 promotes epithelial–mesenchymal transition by acting as a ceRNA of miR‐140‐5p in hepatocellular carcinoma cells; and Wang et al () reported that lncRNA related to periodontitis interacts with miR‐182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients. In our present study, we provide evidence that PVT1 may also function as ceRNA to competitively sponge miR‐448 and affect its distribution on specific targets.…”

Identification of novel key lncRNAs involved in periodontitis by weighted gene co‐expression network analysis

“…PDLSCs are used in periodontal tissue regeneration engineering, periodontal defect repair and gene therapy and have multidirectional differentiation and self‐renewal potential. Because of the development of high‐throughput sequencing technologies, an increasing number of non‐coding RNAs have been found to play an important role in the progression of chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis . By constructing a WGCNA network and calculating the co‐expression relationships between molecules, we can identify the hub genes in the module and provide an overview of the hub gene‐related expression profiles and gene function relationships.…”

“…Several studies have shown that lncRNA can act as a miRNA sponge that regulates miRNA‐targeted mRNA expression. It has been reported that lncRNA‐POIR promotes the expression of FoxO1 through the competitive binding of miR‐182 to increase bone formation by PDLSCs . Peng et al found that lncRNA‐ANCR can upregulate Notch2 by competitively binding miRNA‐758 and inhibiting bone formation by periodontal ligament stem cells .…”

“…such as rheumatoid arthritis and periodontitis. [20][21][22] By constructing a WGCNA network and calculating the co-expression relationships between molecules, we can identify the hub genes in the module and provide an overview of the hub gene-related expression profiles and gene function relationships. In our study, we used the GSE16134 expression profile, which included 241 gingival tissue samples obtained from 120 patients with periodontitis and 69 healthy gingival tissue samples as controls.…”

Lnc‐NTF3‐5 promotes osteogenic differentiation of maxillary sinus membrane stem cells via sponging miR‐93‐3p

“…14 Huang et al revealed a H19/miR-675/TGF-b1/Smad3/HDAC pathway in regulating osteogenic differentiation of human MSCs. 15 In addition, lncRNA-POIR 16 and MEG3 17 were reported to regulate osteogenic differentiation through different mechanisms, whereas knockdown of HoxA-AS3 expression enhanced osteogenic differentiation and osteogenesis markers expression in MSCs. 18 These studies implied that lncRNAs both positively and negatively control the differentiation state of stem cells.…”