Inhibition of lncRNA <i>MIR31HG</i> Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells

Jin, Chanyuan; Jia, Lingfei; Huang, Yiping; Zheng, Yunfei; Du, Ning; Liu, Yunsong; Zhou, Yongsheng

doi:10.1002/stem.2439

Cited by 93 publications

(86 citation statements)

References 59 publications

(79 reference statements)

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“…It has been reported that miR‐31a‐5p negatively regulates skeletogenesis and osteogenesis (Deng, Wu et al., 2013; Jin et al., 2016; Stepicheva, & Song, 2015; Weilner et al., 2016). Previous studies also demonstrated that decreased stemness and increased senescence are the primary causes of declines in osteogenic differentiation of BMSCs (Fehrer, & Lepperdinger, 2005; Zhou et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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“…Whether lncRNA-ANCR also plays an inhibitory role during osteogenic differentiation of ASCs requires further research. Recently, the Zhou group [23] reported that lncRNA-MIR31HG was induced by nuclear factor (NF)-κB activation in human ASCs and that lncRNA-MIR31HG, in turn, contributed to NF-κB activation, which further inhibited bone formation under inflammatory conditions. More importantly, in our current study, we found that lncRNA-MIR31HG was significantly downregulated (Fold change: 2.31, P = 0.000066) in osteogenic differentiated human ASCs when compared with undifferentiated cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggested that lncRNAs play important roles in MSC differentiation, including several publications that investigated the expression and potential role of lncRNAs in the osteogenesis of human BMSCs, mouse C3H10T1/2 MSCs and other types of MSCs [15-22]. Most recently, one study demonstrated an inhibitory role of lncRNA-MIR31HG in osteogenic differentiation of human ASCs under an inflammatory microenvironment [23]. However, there remains a lack of data concerning the global expression and potential function of lncRNAs in the differentiation of human ASCs into osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of Long Non-Coding RNAs in Osteogenic Differentiation of Human Adipose-Derived Stem Cells

Huang¹,

Kang²,

Huang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) play important roles in stem cell differentiation. However, their role in osteogenesis of human adipose-derived stem cells (ASCs), a promising cell source for bone regeneration, remains unknown. Here, we investigated the expression profile and potential roles of lncRNAs in osteogenic differentiation of human ASCs. Methods: Human ASCs were induced to differentiate into osteoblasts in vitro, and the expression profiles of lncRNAs and mRNAs in undifferentiated and osteogenic differentiated ASCs were obtained by microarray. Bioinformatics analyses including subgroup analysis, gene ontology analysis, pathway analysis and co-expression network analysis were performed. The function of lncRNA H19 was determined by in vitro knockdown and overexpression. Quantitative reverse transcription polymerase chain reaction was utilized to examine the expression of selected genes. Results: We identified 1,460 upregulated and 1,112 downregulated lncRNAs in osteogenic differentiated human ASCs as compared with those of undifferentiated cells (Fold change ≥ 2.0, P < 0.05). Among these, 94 antisense lncRNAs, 85 enhancer-like lncRNAs and 160 lincRNAs were further recognized. We used 12 lncRNAs and 157 mRNAs to comprise a coding-non-coding gene expression network. Additionally, silencing of H19 caused a significantly increase in expression of osteogenesis-related genes, including ALPL and RUNX2, while a decrease was observed after H19 overexpression. Conclusion: This study revealed for the first time the global expression profile of lncRNAs involved in osteogenic differentiation of human ASCs and provided a foundation for future investigations of lncRNA regulation of human ASC osteogenesis.

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“…The probes for FIRRE were designed and obtained from RiboBio (lncRNA FISH Probe Mix, C10920), and the sense strands of probes for FIRRE and a probe to 18s RNA were also provided as the matched negative control and the positive control, respectively. All probes were labeled with Cy3 and hybridization was performed according to the manufacturer's instructions and as previously reported (38). Briefly, SW480 cells were cultured in 35 mm confocal dishes and stimulated with LPS for 4 h. The cells were washed with 13 PBS twice, fixed (10 min with 4% formaldehyde), and permeabilized with 70% ethanol.…”

Section: Fluorescence In Situ Hybridizationmentioning

confidence: 99%

The NF-κB–Responsive Long Noncoding RNA FIRRE Regulates Posttranscriptional Regulation of Inflammatory Gene Expression through Interacting with hnRNPU

Liu

Xie

et al. 2017

The Journal of Immunology

110

115

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Long noncoding RNAs, a newly identified class of noncoding RNAs, are important regulators of gene expression in innate immunity. We report in this study that the transcription of FIRRE, a conserved long noncoding RNA between humans and mice, is controlled by NF-κB signaling in macrophages and intestinal epithelial cells. Functionally, FIRRE appears to positively regulate the expression of several inflammatory genes in macrophages or intestinal epithelial cells in response to LPS stimulation via posttranscriptional mechanisms. Specifically, FIRRE physically interacts with heterogeneous nuclear ribonucleoproteins U, regulating the stability of mRNAs of selected inflammatory genes through targeting the AU-rich elements of their mRNAs in cells following LPS stimulation. Therefore, our data indicate a new regulatory role for NF-κB–responsive FIRRE in the posttranscriptional regulation of inflammatory genes in the innate immune system.

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Inhibition of lncRNA MIR31HG Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells

Cited by 93 publications

References 59 publications

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

Identification and Characterization of Long Non-Coding RNAs in Osteogenic Differentiation of Human Adipose-Derived Stem Cells

The NF-κB–Responsive Long Noncoding RNA FIRRE Regulates Posttranscriptional Regulation of Inflammatory Gene Expression through Interacting with hnRNPU

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