MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Ko, Jih‐Yang; Lee, Mel S.; Lian, Wei; Weng, Wen-Tsan; Sun, Yi-Chih; Chen, Yu‐Shan; Wang, Feng‐Sheng

doi:10.1038/s41598-017-03616-w

Cited by 49 publications

(52 citation statements)

References 51 publications

(60 reference statements)

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“…The miR-29 family is highly expressed in human cartilage during end-stage OA and immediately after destabilization of the medial meniscus (DMM) surgery in mice, highlighting its involvement in early disease and maintaining articular cartilage homeostasis (107). However, miR-29 expression is diminished in end-stage knee OA synovium and associates with synovial lining hypertrophy, inflammation, and fibrosis (108). Intra-articular miR-29a injection maintains synovial homeostasis by targeting VEGF and inhibiting OA-related angiogenesis.…”

Section: Synovial Membrane Contribution To Joint Pathology Via Mirsmentioning

confidence: 99%

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

et al. 2018

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The disabling degenerative disease osteoarthritis (OA) is prevalent among the global population. Articular cartilage degeneration is a central feature of OA; therefore, a better understanding of the mechanisms that maintain cartilage homeostasis is vital for developing effective therapeutic interventions. MicroRNAs (miRs) modulate cell signaling pathways and various processes in articular cartilage via posttranscriptional repression of target genes. As dysregulated miRs frequently alter the homeostasis of articular cartilage, modulating select miRs presents a potential therapeutic opportunity for OA. Here, we review key miRs that have been shown to modulate cartilage-protective or -destructive mechanisms and signaling pathways. Additionally, we use an integrative computational biology approach to provide insight into predicted miR gene targets that may contribute to OA pathogenesis, and highlight the complexity of miR signaling in OA by generating both unique and overlapping gene targets of miRs that mediate protective or destructive effects. Early OA detection would enable effective prevention; thus, miRs are being explored as diagnostic biomarkers. We discuss these ongoing efforts and the applicability of miR mimics and antisense inhibitors as potential OA therapeutics.

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Section: Synovial Membrane Contribution To Joint Pathology Via Mirsmentioning

confidence: 99%

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

et al. 2018

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“…103,121,137,157,165 However, two of these studies did did show an up-regulation of the miRNA of interest following cartilage extraction and qPCR. 121,157 To date, it is still challenging to carry out in situ hybridization for detection of miRNAs in vivo. However, other studies have demonstrated successful lentiviral uptake by chondrocytes in murine articular cartilage following intra-articular injection.…”

Section: Approaches To Modulate Mirna Function In Vivomentioning

confidence: 94%

“…None of the studies referenced in this review showed over-expression or inhibition of the miRNA of interest in situ in rodent cartilage following intra-articular injection of specific lentiviral constructs. 103,121,137,157,165 However, two of these studies did did show an up-regulation of the miRNA of interest following cartilage extraction and qPCR. 121,157 To date, it is still challenging to carry out in situ hybridization for detection of miRNAs in vivo.…”

Section: Approaches To Modulate Mirna Function In Vivomentioning

confidence: 95%

“…In addition, intra-articular administration of lentiviruses expressing pre-miR-29a, following collagenase-induced knee joint aggravation in mice, ameliorated synovial angiogenesis and fibrosis thereby slowing down joint destruction. 121 One mechanism by which miR-29a is predicted to modulate synovitis is by suppression of VEGF. This study suggests a potential therapeutic advantage to over-expressing miR-29a in OA knee joints.…”

Section: O T H E R F U N C T I O N a L M I R N A S W I T H T H E R A mentioning

confidence: 99%

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MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

McAlinden

2017

Journal Orthopaedic Research

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MicroRNAs (miRNAs) are small non-coding RNAs that function to control many cellular processes by their ability to suppress expression of specific target genes. Tens to hundreds of target genes may be affected by one miRNA, thereby resulting in modulation of multiple pathways in any given cell type. Therefore, altered expression of miRNAs (i.e., during tissue development or in scenarios of disease or cellular stress) can have a profound impact on processes regulating cell differentiation, metabolism, proliferation, or apoptosis, for example. Over the past 5-10 years, thousands of reports have been published on miRNAs in cartilage and bone biology or disease, thus highlighting the significance of these non-coding RNAs in regulating skeletal development and homeostasis. For the purpose of this review, we will focus on miRNAs or miRNA families that have demonstrated function in vivo within the context of cartilage, bone or other orthopaedicrelated tissues (excluding muscle). Specifically, we will discuss studies that have utilized miRNA transgenic mouse models or in vivo approaches to target a miRNA with the aim of altering conditions such as osteoarthritis, osteoporosis and bone fractures in rodents. We will not discuss miRNAs in the context skeletal cancers since this topic is worthy of a review of its own. Overall, we aim to provide a comprehensive description of where the field currently stands with respect to the therapeutic potential of specific miRNAs to treat orthopaedic conditions and current technologies to target and modify miRNA function in vivo. KeywordsMicroRNAs (miRNAs); cartilage; bone; skeletal development; osteoarthritis MicroRNA (miRNAs) are small non-coding RNA molecules (typically 19-24 nucleotides in length) that function in RNA silencing and post-transcriptional regulation (suppression) of gene expression. 1 While the majority of miRNAs are located within the cell, some miRNAs, commonly known as circulating miRNA or extracellular miRNA, have also been detected outside the cell in the extracellular matrix, in various biological fluids, or in cell culture. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript miRNAs were first discovered over 20 years ago in the nematode Caenorhabditis elegans with the identification of the developmental regulator lin-4. 3 Since then, thousands of miRNAs have been identified and investigated, with a wide distribution in animals, plants, and viruses. 4 MicroRNAs are ubiquitously expressed in different organisms, and many of them are phylogenetically conserved. 5 To date, over 28,000 miR-NAs from various species are listed in the miRBase website (http://www.mirbase.org). Specifically, 2,588 mature miRNAs have been identified in humans and 1,915 mature miRNAs have been reported in mice.With respect to miRNA biosynthesis, transcription of miRNA genes that are located either intergenically or intragenically is mediated primarily by RNA polymerase II in eukaryotes, although RNA polymerase III has also been shown to transcrib...

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“…In nasopharyngeal carcinoma, VEGF was proved to be one of the downstream genes of miR-29a by database prediction and dual luciferase reporter gene [12]. After transfection of miR-29a, luminescence reactions of VEGF 3'-UTR luciferase reporter were statistically down-regulated [13]. Therefore, we wonder if similar regulatory effect exists in HCC.…”

Section: Introductionmentioning

confidence: 99%

miR-29a overexpresion induces apoptosis through targeting VEGF in hepatocellular carcinoma

Wang¹,

Wu²,

Yuan³

et al. 2020

Preprint

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Background : This study aimed to explore the role of miR-29a in hepatocellular carcinoma (HCC) cells. Further, to confirm whether miR-29a targetes vascular endothelial growth factor (VEGF) in HCC cells. Methods: Cell counting Kit-8 (CCK8) and clone formation assay were used to analyze the proliferation of HCC cells. Flow cytometry was performed to analyze the apoptosis and cell cycle of HCC cells. Western blot was used to analyze the expression of Bax, B-cell lymphoma-2 (Bcl-2), cyclin dependent kinase 4 (CDK4), CyclinD1, Retinoblastoma (Rb), p53 and myeloid cell leukemia-1 (MCL1). The targeting relations between miR-29a and VEGF was measuered by dual luciferase assay. Results : Overexpression of miR-29a could distinctly inhibit the proliferation and promote apoptosis of HCC cells. Overexpression of miR-29a obviously up-regulated the expressions of Bax and Rb, and reduced the expressions of CDK4, Bcl-2, Cyclin D1, p53, MCL1 and VEGF in HCC cells. Dual luciferase assay proved that VEGF was the target of miR-29a. Rescue experiments showed that miR-29a targeted VEGF to regulate the proliferation and apoptosis in HCC cells. Conclusions : These results indicated overexpression of miR-29a inhibited the HCC cells proliferation through targeting VEGF.

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MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Cited by 49 publications

References 51 publications

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

miR-29a overexpresion induces apoptosis through targeting VEGF in hepatocellular carcinoma

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