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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 ?-catenin and inhibiting the canonical Wnt pathway. Finally, inflammation increases miR-182 expression through the nuclear factor-?B 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.

SUBMITTER: Wang L

PROVIDER: S-EPMC5108307 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Wang L L Wu F F Song Y Y Li X X Wu Q Q Duan Y Y Jin Z Z

Cell death & disease 20160811 8

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 pati ...[more]

PMID: 27512949

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Project description:BackgroundAn increasing number of studies have shown that dysregulated miR-589-3p is associated with multiple diseases. However, the role of miR-589-3p in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. This study aimed to explore the biological function and potential molecular mechanism of miR-589-3p in osteogenic differentiation of PDLSCs.MethodsGSE159508 was downloaded from Gene Expression Omibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ). Differentially expressed miRNAs between osteogenic induction PDLSCs versus non-induction PDLSCs were obtained by R software. miR-589-3p mimic and miR-589-3p inhibitor and corresponding negative control were obtained and to identify the role of miR-589-3p in osteogenic differentiation of PDLSCs. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. The targeted binding relationship between miR-589-3p and ATF1 was predicted and verified by target prediction analysis and dual-luciferase assay. Furthermore, the functional mechanism based on miR-589-3p and ATF1 in osteogenic differentiation of PDLSCs was further investigated through rescue experiments.ResultsAccording to the cut-off criteria with log 2 FC > 1.0 and P < 0.05, 514 differentially expressed miRNAs were identified between osteogenic induction and non-induction PDLSCs, including 309 upregulated miRNAs and 205 downregulated miRNAs. Compared with control PDLSCs, miR-589-3p expression level was notably increased in PDLSCs that underwent osteogenic induction. The overexpression of miR-589-3p promoted the cell viability of PDLSCs, while the low expression of miR-589-3p had the opposite effect. The dual luciferase reporter assay verified that ATF1 was proved to be a direct target of miR-589-3p in PDLSCs. And overexpressed miR-589-3p reduced the expression of ATF1. Overexpression of miR-589-3p enhanced the osteogenic capacity of PDLSCs, as demonstrated by increases in ALP activity, matrix mineralization, and RUNX2, OCN and OSX expression. In addition, the rescue experiments confirmed that overexpressed ATF1 restored the effects of overexpressed miR-589-3p on cell proliferation and osteogenic differentiation of PDLSCs.ConclusionmiR-589-3p could down-regulate the expression of ATF1, thereby promote the proliferation and osteogenic differentiation of PDLSCs. This finding may provide a new therapeutic target for molecular therapy of periodontitis.

Dataset Information

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

Publications

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

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