LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214

Wang, Cheng‐Gong; Zhan, Lin; Xiao, Han; Liu, Hua; Hu, Yihe; Liao, Qiande; Zhong, Da

doi:10.1016/j.yexmp.2019.01.012

“…For instance, LINC00707 has been shown to stimulate osteogenesis through promoting Wnt2B expression by functioning as ceRNA for microRNA‐370‐3p 20 . LncRNA KCNQ1OT1 contains functional miR‐214 target sites and can promote BMP2 expression to control osteogenic differentiation 21 …”

Section: Introductionmentioning

confidence: 99%

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

Cao

¹

,

Liu

²

,

Zhong

³

et al. 2020

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Objectives: Increasing evidences suggest that inducing mesenchymal stem cells to differentiate into osteoblasts has been as an especially important component in the prevention and therapy for degenerative bone disease. Here, we identify a novel lncRNA, linc02349, which increases significantly during osteogenic differentiation. Materials and methods:Human umbilical cord-derived stem cells (hUC-MSCs) and dental pulp mesenchymal stem cells were used. Overexpression and knockdown of linc02349 in cell lines were generated using lentiviral-mediated gene delivery method.Bioinformatics prediction, Ago2-RIP assay and dual-luciferase reporter system were employed to examine miRNA which interacts with linc02349. The RNA FISH assay was performed to identify the subcelluar location of linc02349. Alizarin Red S staining, ALP staining and qPCR were applied to identify the osteogenic differentiation. The potential linc02349-regulated genes, miR-25-3p and miR-33b-5p, were explored by ChIP, RIP and Western blotting assays. Micro-CT was used to measure the osteogenic content in bone formation assay in vivo. Results: Linc02349 overexpression improves osteogenic differentiation by in vitroand in vivo analysis. Mechanistically, linc02349 acts as a molecular sponge for miR-25-3p and miR-33b-5p to control expression abundance of SMAD5 and Wnt10b,

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“…However, the role of lncRNA LOC100506178 on the osteogenic differentiation process of BMSCs known little. LncRNA HOTAIRM1 was identified as a critical regulator to promote osteogenesis of MSCs though positively modulates the activity of JNK and c-Jun signaling pathway (Liu et al, 2019). Zheng et al (2019) found that lncRNA MALAT1 suppressed osteogenic differentiation of BMSCs via regulating the MAPK signaling pathway-related proteins extracellular signal-regulated kinase 1/2 (ERK1/2) and P38.…”

Section: Discussionmentioning

confidence: 99%

LncRNA LOC100506178 promotes osteogenic differentiation via regulating miR-214-5p-BMP2 axis in human bone marrow mesenchymal stem cells

Li

¹

,

Fang

²

,

Liu

³

et al. 2020

PeerJ

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Osteogenic differentiation is an important role in dental implantation. Long no coding RNAs (lncRNAs) are a novel class of noncoding RNAs that have significant effects in a variety of diseases. However, the function and mechanisms of LOC100506178 in osteogenic differentiation and migration of bone morphogenetic protein 2 (BMP2)induced osteogenic differentiation of human bone marrow mesenchymalstem cells (hBMSCs) remain largely unclear. BMP2 was used to induce osteogenic differentiation of hBMSCs. Quantitative real time PCR (qRT-PCR) was used to examine the expression of LOC100506178, miR-214-5p, Runt-related transcription factor 2 (RUNX2), Osterix (Osx), and Alkaline Phosphatase (ALP) in BMP2-induced osteogenic differentiation of hBMSCs. The function of LOC100506178 and miR-214-5p was explored in vitro using Alizarin Red S Staining, ALP activity, as well as in vivo ectopic bone formation. Luciferase reporter assay was performed to assess the association between LOC100506178 and miR-214-5p, as well as miR-214-5p and BMP2. The miR-214-5p sponging potential of LOC100506178 was evaluated by RNA immunoprecipitation. In the present study, the expression of LOC100506178 was found to be increased in BMP2induced osteogenic differentiation of hBMSCs, accompanied with decreased miR-214-5p expression and increased RUNX2, Osx and ALP expression. LOC100506178 significantly induced, while miR-214-5p suppressed the BMP2-induced osteogenic differentiation of hBMSCs. Mechanistically, LOC100506178 was directly bound to miR-214-5p and miR-214-5p targeted the 3 -untranslated region of BMP2 to negatively regulate its expression. In conclusion, our data indicate a novel molecular pathway LOC100506178/miR-214-5p/BMP2 in relation to hBMSCs differentiation into osteoblasts, which may facilitate bone anabolism. Subjects Biochemistry, Cell Biology How to cite this article Li L, Fang J, Liu Y, Xiao L. 2020. LncRNA LOC100506178 promotes osteogenic differentiation via regulating miR-214-5p-BMP2 axis in human bone marrow mesenchymal stem cells. PeerJ 8:e8909 http://doi.org/10.7717/peerj.8909 Li et al. (2020), PeerJ, DOI 10.7717/peerj.8909 2/15 Li et al. (2020), PeerJ, DOI 10.7717/peerj.8909 3/15 Li et al. (2020), PeerJ, DOI 10.7717/peerj.8909 7/15 Li et al. (2020), PeerJ, DOI 10.7717/peerj.8909 9/15 Li et al. (2020), PeerJ, DOI 10.7717/peerj.8909 10/15 Li et al. (2020), PeerJ, DOI 10.7717/peerj.8909 12/15 Al-Almaie S, Kavarodi AM, Al Faidhi A. 2013. Maxillary sinus functions and complications with lateral window and osteotome sinus floor elevation procedures followed by dental implants placement: a retrospective study in 60 patients. . 2016. MiR-34a promotes osteogenic differentiation of human adipose-derived stem cells via the RBP2/NOTCH1/CYCLIN D1 coregulatory network. Stem Cell Reports 7:236-248 Sang Q. 2017. miR-214 suppresses the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and these effects are mediated through the inhibition of the JNK and p38 pathways. Du J, Fan Z. 2013. Shh signaling, negatively regulated by...

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“…Previously studies have shown that the expression of miR-214 is significantly decreased during osteogenic induction. First, overexpression of miR-214 inhibits BMP2 expression by binding to its 3'UTR; whereas, overexpression of lncRNA KCNQ1OT1 increased BMP2 expression by suppressing miR-214 expression to promote osteogenic differentiation of BMSCs (Wang et al 2019). Subsequently, overexpression of miR-214 inhibits osteoblast differentiation of BMSCs by suppressing ALP activity and gene expression of OCN, type I collagen (Col I), and osteopontin (OPN) and also inhibiting JNK and p38 pathways (Guo et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "LncRNA LOC100506178 promotes osteogenic differentiation via regulating miR-214-5p-BMP2 axis in human bone marrow mesenchymal stem cells (v0.1)"

2020

0

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Osteogenic differentiation is an important role in dental implantation. Long no coding RNAs (lncRNAs) are a novel class of noncoding RNAs that have significant effects in a variety of diseases. However, the function and mechanisms of LOC100506178 in osteogenic differentiation and migration of bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation of human bone marrow mesenchymalstem cells (hBMSCs) remain largely unclear. BMP2 was used to induce osteogenic differentiation of hBMSCs. Quantitative real time PCR (qRT-PCR) was used to examine the expression of LOC100506178, miR-214-5p, Runt-related transcription factor 2 (RUNX2), Osterix (Osx), and Alkaline Phosphatase (ALP) in BMP2-induced osteogenic differentiation of hBMSCs. The function of LOC100506178 and miR-214-5p was explored in vitro using Alizarin Red S Staining, ALP activity, as well as in vivo ectopic bone formation. Luciferase reporter assay was performed to assess the association between LOC100506178 and miR-214-5p, as well as miR-214-5p and BMP2. The miR-214-5p sponging potential of LOC100506178 was evaluated by RNA immunoprecipitation. In the present study, the expression of LOC100506178 was found to be increased in BMP2-induced osteogenic differentiation of hBMSCs, accompanied with decreased miR-214-5p expression and increased RUNX2, Osx and ALP expression. LOC100506178 significantly induced, while miR-214-5p suppressed the BMP2-induced osteogenic differentiation of hBMSCs. Mechanistically, LOC100506178 was directly bound to miR-214-5p and miR-214-5p targeted the 3'-untranslated region of BMP2 to negatively regulate its expression. In conclusion, our data indicate a novel molecular pathway LOC100506178/miR-214-5p/BMP2 in relation to hBMSCs differentiation into osteoblasts, which may facilitate bone anabolism.

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LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214

Cited by 99 publications

References 30 publications

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

LncRNA LOC100506178 promotes osteogenic differentiation via regulating miR-214-5p-BMP2 axis in human bone marrow mesenchymal stem cells

Peer Review #2 of "LncRNA LOC100506178 promotes osteogenic differentiation via regulating miR-214-5p-BMP2 axis in human bone marrow mesenchymal stem cells (v0.1)"

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