Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells

Xia, Zhuying; Hu, Yingyao; Xie, Pingli; Tang, Siyuan; Luo, Xi; Liao, Er-Yuan; Chen, Fei; Xie, Hui

doi:10.1155/2015/624037

Cited by 49 publications

(58 citation statements)

References 33 publications

(34 reference statements)

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“…Key miRNAs are miR-6090, which may play a role in embryo development 62; miR-4516, which is involved in autophagy63; miR-3960, which is related to Runx264, and miR-4459, which is involved in altering the stemness of embryonic stem cells65. However, the relationship between these microRNAs and chondrocytes remains unknown and needs to be further researched.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

et al. 2017

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OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p. Exosomes derived from SMSCs or SMSC-140s (SMSC-Exos or SMSC-140-Exos) were isolated and identified. Proliferation, migration and ECM secretion were measured in vitro and compared between groups. The mechanism involving alternative Wnt signalling and activation of Yes-associated protein (YAP) was investigated using lentivirus, oligonucleotides or chemical drugs. The preventative effect of exosomes in vivo was measured using Safranin-O and Fast green staining and immunohistochemical staining. RESULTS: Wnt5a and Wnt5b carried by exosomes activated YAP via the alternative Wnt signalling pathway and enhanced proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion. Highly-expressed miR-140-5p blocked this side-effect via RalA. SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC-140-Exos successfully prevented OA in a rat model. CONCLUSIONS: These findings highlight the promising potential of SMSC-140-Exos in preventing OA. We first found a potential source of exosomes and studied their merits and shortcomings. Based on our understanding of the molecular mechanism, we overcame the shortcomings by modifying the exosomes. Such exosomes derived from modified cells hold potential as future therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

et al. 2017

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“…They reported that miR-3960 and miR-2861, transcribed together from the same miRNA polycistron, both function in osteoblast differentiation through a novel Runx2/miR-3960/miR-2861regulatory feedback loop [70]. Xia et al showed that Runx2/miR-3960/miR-2861 positive feedback loop plays an important role in osteogenic transdifferentiation of vascular smooth muscle cells [71]. Our findings showed that miR-2861 and miR-3960 have increased expression in both chronic and active group compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

et al. 2016

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Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p <0.05 or fold change > 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis.

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“…Further, it has been reported that activation of RUNX2 induces the overexpression of miR-3960 and miR-3960, which promotes the vascular calcification by increasing the osteoblast differentiation markers alkaline phosphatase (ALP) and osteocalcin [68]. Considering together the above-results suggest that overexpression of TGFβ2-OT1 and subsequent downregulation of miR-3960 may prove a novel way to specifically target RUNX2 signaling in the pathology of atherosclerosis and vascular calcification [65, 68]. Moreover, in vitro studies in human THP-1 foam cells indicate that upregulation of lncRNA nuclear factor 1A-AS1 (NF1A-AS1) leads to reduced expression of nuclear factor 1A (NF1A).…”

Section: Lncrna and Vascular Pathologiesmentioning

confidence: 99%

LncRNA as a Therapeutic Target for Angiogenesis

Kumar

Goyal

2017

CTMC

212

152

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Background: Out of 3 billion base pairs in human genome only ~2% code for proteins; and out of 180,000 transcripts in human cells, about 20,000 code for protein, remaining 160,000 are non-coding transcripts. Most of these transcripts are more than 200 base pairs and constitute a group of long non-coding RNA (lncRNA). Many of the lncRNA have its own promoter, and are well conserved in mammals. Accumulating evidence indicates that lncRNAs act as molecular switches in cellular differentiation, movement, apoptosis, and in the reprogramming of cell states by altering gene expression patterns. However, the role of this important group of molecules in angiogenesis is not well understood. Angiogenesis is a complex process and depends on precise regulation of gene expression. Conclusion:Dysregulation of transcription during this process may lead to several diseases including various cancers. As angiogenesis is an important process in cancer pathogenesis and treatment, lncRNA may be playing an important role in angiogenesis. In support of this, lncRNA microvascular invasion in hepatocellular carcinoma (MVIH) has been shown to activate angiogenesis. Furthermore, lncRNA-Meg3-knockout mouse showed increased expression of vascular endothelial growth factor pathway genes and increased cortical microvessel density. Overall, there is strong evidence that lncRNA is an important class of regulatory molecule, and a number of studies have demonstrated that these can be targeted to change cellular physiology and functions. In this review, we have attempted to summarize these studies and elucidate the potential of this novel regulatory molecule as a therapeutic target.

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Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells

Cited by 49 publications

References 33 publications

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model

MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

LncRNA as a Therapeutic Target for Angiogenesis

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