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

Huang, Guangxin; Kang, Yan; Huang, Zhiyu; Zhang, Zhiqi; Meng, Fangang; Chen, Weishen; Fu, Ming; Liao, Weiming; Zhang, Ziji

doi:10.1159/000478751

Cited by 45 publications

(50 citation statements)

References 42 publications

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“…34 In hADSCs osteogenic differentiation, the differentially expressed lncRNAs were also identified, and lncRNA H19 was found to significantly influence the expression of osteogenesis-related genes ALPL and Runx2. 4 Our results further confirmed that lncRNAs have a great impact on osteogenic differentiation as their sponging effects on miRNAs could mediate the expressions of osteogenesis-related mRNAs.…”

Section: Discussionsupporting

confidence: 77%

“…Through bioinformatics analysis, Gu et al identified 147 lncRNAs totally that were predicted to interact with miRNAs and compete for miRNA binding sites with mRNAs in osteogenic differentiation of periodontal ligament stem cells, revealing the potential lncRNA ceRNA networks . In hADSCs osteogenic differentiation, the differentially expressed lncRNAs were also identified, and lncRNA H19 was found to significantly influence the expression of osteogenesis‐related genes ALPL and Runx2 . Our results further confirmed that lncRNAs have a great impact on osteogenic differentiation as their sponging effects on miRNAs could mediate the expressions of osteogenesis‐related mRNAs.…”

Section: Discussionsupporting

confidence: 75%

“…As an important cell type, they possess great potential to be applied to cell‐based therapies. Recent studies have indicated that hADSCs can serve as an alternative cell source to birth bone marrow mesenchymal stem cells (BMSCs), the cell source for bone regeneration . The proliferative abilities and osteogenic differentiation capabilities of BMSCs decreased with age and osteoporosis, whereas hADSCs showed consistent osteogenic differentiation capability despite of old age and osteoporotic conditions .…”

Section: Introductionmentioning

confidence: 99%

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LncRNA‐PCAT1 targeting miR‐145‐5p promotes TLR4‐associated osteogenic differentiation of adipose‐derived stem cells

et al. 2018

J Cellular Molecular Medi

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This study was aimed to explore the differential expression of long noncoding RNAs (lncRNA)‐PCAT1, miR‐145‐5p and TLR4 in osteogenic differentiation via the Toll‐like receptor (TLR) signalling pathway and consequently determine the potential molecular mechanism. The mRNAs and pathways related to the osteogenic differentiation in human adipose‐derived stem cells (hADSCs) were analysed by bioinformatics. The MiRanda and TargetScan database were employed to detect the potential binding sites of miRNAs on lncRNAs and mRNAs. The differential expression of lncRNA‐PCAT1, miR‐145‐5p and TLR4 were detected by qRT‐PCR. Rrelated protein expression was analysed by Western blot. The targeted relationships between lncRNA‐PCAT1, miR‐145‐5p and TLR4 were verified by dual‐luciferase reporter assay. Alkaline phosphatase (ALP) activity and ARS staining assays were used to measure the impacts exerted by lncRNA PCAT1, miR‐145‐5p and TLR4 mRNA on osteogenic differentiation. After the induction of osteoblast differentiation, the expression of lncRNA‐PCAT1 and TLR4 increased, while the expression of miR‐145‐5p decreased. Dual‐luciferase reporter assay confirmed the targeted relationship between lncRNA‐PCAT1, miR‐145‐5p, and TLR4. LncRNA‐PCAT1 negatively regulated miR‐145‐5p and positively regulated TLR4. Knockdown of lncRNA‐PCAT1 or TLR4 decreased the expression of osteogenic differentiation‐related proteins, reduced the ALP and ARS levels and the activity of the TLR signalling pathway. MiR‐145‐5p could reverse the effects of PCAT1 and TLR4 in hADSCs osteogenic differentiation. LncRNA‐PCAT1 negatively regulated miR‐145‐5p, which promoted TLR4 expression to promote osteogenic differentiation by activating the TLR signalling pathway.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LncRNA‐PCAT1 targeting miR‐145‐5p promotes TLR4‐associated osteogenic differentiation of adipose‐derived stem cells

et al. 2018

J Cellular Molecular Medi

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“…As a family of small (18-22 nucleotide, nt) and endogenous noncoding RNA molecules, miRNAs target specific messenger RNAs and hence play a negative regulatory role in gene expression by triggering the translational repression or degradation of their target genes [13,14].In contrary, lncRNAs belong to a big family of transcribed RNA molecules (over 200 nt) with little potential to code proteins [15,16]. Recent studies have focused on the effects of lncRNAs in atherosclerosis [17]. It was shown that antisense noncoding RNA in the INK4 locus (ANRIL) and lncRNA-H19 are associated with the risk of CAD and atherosclerosis [18].…”

Section: Introductionmentioning

confidence: 99%

Association Between the Deletion Allele of Ins/Del Polymorphism (Rs145204276) in the Promoter Region of GAS5 with the Risk of Atherosclerosis

Shen

Qiang

2018

Cell Physiol Biochem

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Background/Aims: LncRNA is a growth arrest-specific transcript 5 (GAS5) with tumor suppressor activities in some cancers, but its role in atherosclerosis is unclear. Methods: Bioinformatics algorithm analysis was utilized to search the target of GAS5 and miR-21, followed by luciferase assay to confirm these targets. Real-time PCR and western-blot were utilized to verify the connection among GAS5, miR-21 and Programmed cell death 4 (PDCD4). MTT assay and flow cytometry analysis were performed to explore the mechanism of GAS5 in the regulation of atherosclerosis. Results: GAS5 directly targets miR-21 and functions as a competing endogenous RNA to suppress miR-21 expression. We also observed that rs145204276 polymorphism, including INS/INS and DEL/DEL, on GAS5 promoter increased transcription activity of GAS5, but the presence of rs145204276 DEL/DEL allele significantly promoted the transcription of GAS5 promoter compared with rs145204276 INS/INS allele. PDCD4 was predicted as a direct target gene of miR-21 with a binding site on PDCD4 3’UTR. It was further confirmed by luciferase assay that miR-21 significantly reduced the luciferase activity of wild-type PDCD4 3’UTR but not that of mutant PDCD4 3’UTR. In addition, high glucose significantly inhibited the growth rate of EC genotyped as DEL/DEL or INS/ INS, and apparently promoted the apoptotic rate of either DEL/DEL or INS/INS genotype ECs. Furthermore, the effect of high glucose was stronger in the INS/INS group, while the expression of GAS5 was dramatically upregulated with the presence of GAS5 DEL/DEL, while GAS5 positively regulated PDCD4 expression via inhibiting miR-21 expression. GAS5 siRNA and miR-21 mimics significantly decreased GAS5 and PDCD4 expressions, and the inhibitory effects of GAS5 siRNA or miR-21 mimics on GAS5 and PDCD4 expressions in the INS/INS group was stronger. Moreover, GAS5 siRNA and miR-21 mimics remarkably triggered cells proliferation and suppressed cell apoptosis, and the inhibition effects of GAS5 siRNA or miR-21 mimics on either cell viability and apoptosis in the INS/INS group was stronger. In this study, we enrolled 1,306 subjects with or without atherosclerosis and found that the INS/DEL or DEL/DEL genotypes significantly decreased the risk of atherosclerosis compared with the ins/ins genotype (adjusted odds ratio: 0.74 and 0.40, respectively). Conclusion: In summary, rs145204276 was associated with the risk of atherosclerosis by affecting the proliferation and apoptosis of endothelial cells via regulating the GAS5/miR-21/PDCD4 signaling pathway.

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“…Several studies used gene expression microarrays to address osteoblast differentiation. Some focused on osteogenic induction of human adipose-derived stem cells [4] or human bone marrow mesenchymal stem cells [5]. Others used a time series microarray analysis of mineralizing murine primary osteoblast cultures [6].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profiling of murine osteoblast differentiation based on RNA-seq expression analyses

Khayal

Grünhagen

Provazník

et al. 2018

Bone

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Osteoblastic differentiation is a multistep process characterized by osteogenic induction of mesenchymal stem cells, which then differentiate into proliferative pre-osteoblasts that produce copious amounts of extracellular matrix, followed by stiffening of the extracellular matrix, and matrix mineralization by hydroxylapatite deposition. Although these processes have been well characterized biologically, a detailed transcriptional analysis of murine primary calvaria osteoblast differentiation based on RNA sequencing (RNA-seq) analyses has not previously been reported. Here, we used RNA-seq to obtain expression values of 29,148 genes at four time points as murine primary calvaria osteoblasts differentiate in vitro until onset of mineralization was clearly detectable by microscopic inspection. Expression of marker genes confirmed osteogenic differentiation. We explored differential expression of 1386 protein-coding genes using unsupervised clustering and GO analyses. 100 differentially expressed lncRNAs were investigated by co-expression with protein-coding genes that are localized within the same topologically associated domain. Additionally, we monitored expression of 237 genes that are silent or active at distinct time points and compared differential exon usage. Our data represent an in-depth profiling of murine primary calvaria osteoblast differentiation by RNA-seq and contribute to our understanding of genetic regulation of this key process in osteoblast biology.

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

Cited by 45 publications

References 42 publications

LncRNA‐PCAT1 targeting miR‐145‐5p promotes TLR4‐associated osteogenic differentiation of adipose‐derived stem cells

LncRNA‐PCAT1 targeting miR‐145‐5p promotes TLR4‐associated osteogenic differentiation of adipose‐derived stem cells

Association Between the Deletion Allele of Ins/Del Polymorphism (Rs145204276) in the Promoter Region of GAS5 with the Risk of Atherosclerosis

Transcriptional profiling of murine osteoblast differentiation based on RNA-seq expression analyses

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