Identification of synovial fluid microRNA signature in knee osteoarthritis: differentiating early- and late-stage knee osteoarthritis

Li, Y.-H.; Tavallaee, Ghazaleh; Tokár, Tomáš; Nakamura, Akihiro; Sundararajan, Kala; Weston, A.; Sharma, Anjali; Mahomed, N.N.; Gandhi, Rajiv; Jurišica, Igor; Kapoor, Mohit

doi:10.1016/j.joca.2016.04.019

Cited by 99 publications

(105 citation statements)

References 23 publications

(24 reference statements)

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“…miRNAs are endogenous small non-coding RNAs (approximately 22 nts long), which can regulate gene expression post-transcriptionally and have been implicated in various diseases as well as considered as potential biomarkers [6]. It is known that miRNAs play an important role in mediating the effects of the main risk factors for OA, such as aging and inflammation, through control of target genes [7–9].…”

Section: Introductionmentioning

confidence: 99%

Effects of microRNA-146a on the proliferation and apoptosis of human osteoarthritis chondrocytes by targeting TRAF6 through the NF-κB signalling pathway

Zhong

Liu

et al. 2017

Bioscience Reports

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The present study aims to investigate the effects of miR-146a on the proliferation and apoptosis of human osteoarthritis (OA) chondrocytes by targeting tumour necrosis factor receptor-associated factor 6 (TRAF6) through nuclear factor-κB (NF-κB) signalling pathway. Human normal and OA chondrocytes were selected and divided into the normal group, blank group, negative control (NC) group, miR-146a mimics group, miR-146a inhibitors, miR-146a inhibitor + si-TRAF6 group and si-TRAF6 group. Quantitative real-time PCR (qRT-PCR) was applied to detect the expressions of miR-146a, TRAF6 mRNA and NF-κB mRNA. Western blotting was used to detect the protein expressions of TRAF6 and NF-κB. CCK-8 assay and flow cytometry were used to detect cell proliferation and apoptosis. Compared with normal chondrocytes, the expression of miR-146a decreased, while the mRNA and protein expressions of TRAF6 and NF-κB increased in OA chondrocytes. OA chondrocytes had a lower proliferation rate and a higher apoptosis rate than the normal chondrocytes. Compared with the blank, NC and si-TRAF6 groups, the expression of miR-146a increased in the miR-146a mimics group, but decreased in the miR-146a inhibitors and miR-146a inhibitor + si-TRAF6 groups. Compared with the blank, NC and miR-146a inhibitor + si-TRAF6 groups, the mRNA and protein expressions of TRAF6 and NF-κB decreased, cell proliferation rate increased and cell apoptosis rate decreased in the miR-146a mimics and si-TRAF6 groups, while opposite trends were observed in the miR-146a inhibitors group. Our study suggests that miR-146a could promote proliferation and inhibit apoptosis of OA chondrocytes by inhibiting TRAF6 expression and suppressing the activation of NF-κB signalling pathway.

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Section: Introductionmentioning

confidence: 99%

Effects of microRNA-146a on the proliferation and apoptosis of human osteoarthritis chondrocytes by targeting TRAF6 through the NF-κB signalling pathway

Zhong

Liu

et al. 2017

Bioscience Reports

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“…Hypomethylation of the promoter region of miR-23a may contribute to its increased expression, which is observed for both, miR-23a and miR-23b in human hip and knee OA AC compared to healthy AC [151,158]. Yet, another study shows downregulation of miR-23a expression in human knee OA AC explant cultures upon rIL-1β treatment, whereas miR-23 expression and release were enhanced in synovial explants from OA patients [159]. This indicates an opposing scenario in rIL-1β treated ex vivo OA AC cultures compared to the in vivo observed upregulation.…”

Section: Mirna Regulation Of Fibroblast Growth Factor 2 Transformmentioning

confidence: 99%

“…Hydrostatic pressure increases both miR-27a and miR-27b expression specifically in human hip OA AC monolayer cell cultures, but not in cell cultures derived from normal hip AC [168]. Remarkably, though rIL-1β downregulates miR-27a and miR-27b in human late stage knee OA AC explant cultures, in synovial explant cultures of patients with late stage knee OA AC an upregulation and enhanced secretion of miR-27a and miR-27b was detectable upon rIL-1β stimulation [159]. Long non-coding RNA-cartilage injury-related (lncRNA-CIR), which is upregulated in OA AC, acts as a sponge for miR-27, whereas miR-27 directly represses lncRNA-CIR expression [167].…”

Section: Mirna Regulation Of Fibroblast Growth Factor 2 Transformmentioning

confidence: 99%

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

Boehme,

Rolauffs

2018

IJMS

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Osteoarthritis (OA) is a degenerative whole joint disease, for which no preventative or therapeutic biological interventions are available. This is likely due to the fact that OA pathogenesis includes several signaling pathways, whose interactions remain unclear, especially at disease onset. Early OA is characterized by three key events: a rarely considered early phase of proliferation of cartilage-resident cells, in contrast to well-established increased synthesis, and degradation of extracellular matrix components and inflammation, associated with OA progression. We focused on the question, which of these key events are regulated by growth factors, inflammatory cytokines, and/or miRNA abundance. Collectively, we elucidated a specific sequence of the OA key events that are described best as a very early phase of proliferation of human articular cartilage (AC) cells and concomitant anabolic/catabolic effects that are accompanied by incipient pro-inflammatory effects. Many of the reviewed factors appeared able to induce one or two key events. Only one factor, fibroblast growth factor 2 (FGF2), is capable of concomitantly inducing all key events. Moreover, AC cell proliferation cannot be induced and, in fact, is suppressed by inflammatory signaling, suggesting that inflammatory signaling cannot be the sole inductor of all early OA key events, especially at disease onset.

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“…Current version of pathDIP has been already applied (32,33), highlighting the value of predicted pathway associations in pathway enrichment analysis. Furthermore, improved overlap of extended pathways compared with overlap of their core versions (Supplementary Figures S6 and S7) suggests that extended source-specific, same-class pathways converge to similar definitions, highlighting that pathDIP will contribute to consolidation of existing pathways.…”

Section: Future Workmentioning

confidence: 99%

pathDIP: an annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis

et al. 2016

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Molecular pathway data are essential in current computational and systems biology research. While there are many primary and integrated pathway databases, several challenges remain, including low proteome coverage (57%), low overlap across different databases, unavailability of direct information about underlying physical connectivity of pathway members, and high fraction of protein-coding genes without any pathway annotations, i.e. ‘pathway orphans’. In order to address all these challenges, we developed pathDIP, which integrates data from 20 source pathway databases, ‘core pathways’, with physical protein–protein interactions to predict biologically relevant protein–pathway associations, referred to as ‘extended pathways’. Cross-validation determined 71% recovery rate of our predictions. Data integration and predictions increase coverage of pathway annotations for protein-coding genes to 86%, and provide novel annotations for 5732 pathway orphans. PathDIP (http://ophid.utoronto.ca/pathdip) annotates 17 070 protein-coding genes with 4678 pathways, and provides multiple query, analysis and output options.

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Identification of synovial fluid microRNA signature in knee osteoarthritis: differentiating early- and late-stage knee osteoarthritis

Abstract: We provide first evidence of the differential expression of circulating miRNAs in early-stage vs late-stage knee OA-SF. Further, we provide source, release and genes/pathways regulated by identified miRNAs.

Cited by 99 publications

References 23 publications

Effects of microRNA-146a on the proliferation and apoptosis of human osteoarthritis chondrocytes by targeting TRAF6 through the NF-κB signalling pathway

Effects of microRNA-146a on the proliferation and apoptosis of human osteoarthritis chondrocytes by targeting TRAF6 through the NF-κB signalling pathway

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

pathDIP: an annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis

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