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MiR-1827 inhibits osteogenic differentiation by targeting IGF1 in MSMSCs.

ABSTRACT: We recently reported that maxillary sinus membrane stem cells (MSMSCs) have osteogenic potential. However, the biological mechanisms of bone formation remain unclear. In this study, we investigated the role and mechanisms of microRNAs (miRNAs) in the osteogenic differentiation of MSMSCs. The expression of miRNAs was determined in differentiated MSMSCs by comprehensive miRNA microarray analysis and quantitative RT-PCR (qRT-PCR). We selected miR-1827 for functional follow-up studies to explore its significance in MSMSCs. Here, miR-1827 was found to be up-regulated during osteogenic differentiation of MSMSCs. Over expression of miR-1827 inhibited osteogenic differentiation of MSMSCs in vitro, whereas the repression of miR-1827 greatly promoted cell differentiation. Further experiments confirmed that insulin-like growth factor 1 (IGF1) is a direct target of miR-1827. miR-1827 inhibited osteogenic differentiation partially via IGF1, which in turn is a positive regulator of osteogenic differentiation. Moreover, miR-1827 suppressed ectopic bone formation and silencing of miR-1827 led to increased bone formation in vivo. In summary, this study is the first to demonstrate that miR-1827 can regulate osteogenic differentiation. The increase in miR-1827 expression observed during osteogenesis is likely a negative feedback mechanism, thus offering a potential therapeutic target to address inadequate bone volume for dental implantation through inhibiting miR-1827.

SUBMITTER: Zhu S

PROVIDER: S-EPMC5384002 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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miR-1827 inhibits osteogenic differentiation by targeting IGF1 in MSMSCs.

Zhu ShuangXi S Peng Wei W Li Xiang X Weng JunQuan J Zhang Xing X Guo JunBing J Huang DaiYing D Rong Qiong Q Chen SongLing S

Scientific reports 20170407

We recently reported that maxillary sinus membrane stem cells (MSMSCs) have osteogenic potential. However, the biological mechanisms of bone formation remain unclear. In this study, we investigated the role and mechanisms of microRNAs (miRNAs) in the osteogenic differentiation of MSMSCs. The expression of miRNAs was determined in differentiated MSMSCs by comprehensive miRNA microarray analysis and quantitative RT-PCR (qRT-PCR). We selected miR-1827 for functional follow-up studies to explore its ...[more]

PMID: 28387248

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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.

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MiR-1827 inhibits osteogenic differentiation by targeting IGF1 in MSMSCs.

Publications

miR-1827 inhibits osteogenic differentiation by targeting IGF1 in MSMSCs.

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