Integrated Study of Globally Expressed microRNAs in IL-1β-stimulated Human Osteoarthritis Chondrocytes and Osteoarthritis Relevant Genes: A Microarray and Bioinformatics Analysis

Rasheed, Zafar; Al‐Shobaili, Hani A.; Rasheed, Naila; Salloom, Abdulaziz A M Al; Al-Shaya, Osama; Mahmood, Amer; Alajez, Nehad M.; Alghamdi, Ahmad M.; Mehana, El-Sayed E.

doi:10.1080/15257770.2016.1163380

Cited by 25 publications

(19 citation statements)

References 26 publications

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“…In the current study, we found that miR-193a-3p was downregulated in OA cartilage tissue and chondrocytes, which was in agreement with a previous report (Rasheed et al, 2016). In addition, the upregulation of miR-193a-3p inhibited the expression of IL-6, IL-1β, TNF-α, IL-8, MMP-3, MMP-13, and ADAMTS-5, as well as apoptotic rate, while promoting the expression of ACAN and Col2a1 in human chondrocytes.…”

Section: Discussionsupporting

confidence: 94%

“…Certain miRNAs exert their role in OA by targeting OA‐related genes, such as MMP‐13, interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), NOS2, or BMPR2, or targeting OA‐associated signaling pathways, such as MAPKs, DUSPs, JAK‐STAT. MiR‐193a‐3p expression was downregulated in IL‐1β‐treated and untreated human OA chondrocytes (Rasheed et al, ). The specific role of miR‐193a‐3p in the regulation of pro‐inflammatory cytokines, apoptosis, and production of the ECM in OA chondrocytes is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

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NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

Yang

et al. 2020

Cell Biology International

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Long non‐coding RNAs (lncRNAs) were reported to be involved in the progression of osteoarthritis (OA). The aim of this work was to explore the functional role of lncRNA nuclear‐enriched abundant transcript 1 (NEAT1) in OA. Reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) was employed to analyze the expression of microRNA (miR‐193a)‐3p, NEAT1, and sex‐determining region Y‐box protein 5 (SOX5), as well as the levels of pro‐inflammatory cytokines interleukin‐6 (IL‐6), IL‐1β, tumor necrosis factor‐α (TNF‐α), and IL‐8 in OA cartilage tissue and chondrocytes. In addition, flow cytometry was used to measure the apoptosis of chondrocytes. The protein levels of extracellular matrix ACAN, collagen type II α1 chain (Col2a1), matrix metalloproteinase‐3 (MMP‐3), MMP‐13, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)‐5 and SOX5 were determined using western blot analysis. Dual‐luciferase reporter assay was performed to determine the target relationship among NEAT1, miR‐193a‐3p, and SOX5. We found that miR‐193a‐3p expression was downregulated, while NEAT1 and SOX5 were upregulated in OA cartilage tissue and chondrocytes. Both upregulation of miR‐193a‐3p and knockdown of NEAT1 suppressed inflammation, apoptosis, and reduced the protein levels of MMP‐3, MMP‐13, and ADAMTS‐5, while elevating ACAN and Col2a1 expression in chondrocytes. NEAT1 targeted miR‐193a‐3p, and SOX5 was targeted by miR‐193a‐3p. Silencing of miR‐193a‐3p reversed the NEAT1 knockdown‐mediated effect on the inflammation, apoptosis, and production of the extracellular matrix. The introduction of SOX5 abolished the impact of the upregulation of miR‐193a‐3p on inflammation, apoptosis, and production of extracellular matrix in chondrocytes. In conclusion, NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human OA.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

Yang

et al. 2020

Cell Biology International

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“…27 More recently, research studies have highlighted the involvement of miRNAs in the development of OA. 28,29 However, detailed studies regarding miRNAs and their downstream molecular mechanism underlying the progression of OA remain very limited. Hence, the current study aimed to explore the molecular mechanism associated with miR-27b-3p in OA.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA‐27b‐3p relieves osteoarthritis pain via regulation of KDM4B‐dependent DLX5

Zhang

Zhou

et al. 2020

BioFactors

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Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR-27b-3p in the development of OA. The expression of miR-27b-3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR-27b-3p was found in both of the samples. To further explore the miR-27b-3p functions in OA, western blot analysis, enzyme-linked immunosorbent assay, and β-galactosidase activity assay were conducted with the results showing that knockdown of miR-27b-3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR-27b-3p, lysine Demethylase 4B (KDM4B), and Distal-Less Homeobox 5 (DLX5) identified using dual-luciferase reporter gene assay and ChIP assay revealed that miR-27b-3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR-27b-3p silencing. In conclusion, suppression of miR-27b-3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.

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“…A microarray-based analysis of miRNAs in human OA chondrocytes, stimulated by IL-1β, showed that the expression of 36 miRNAs were altered, with the majority of them (35 out of 36) being downregulated and affecting inflammatory networks [88]. …”

Section: Mirna-associated Pathways In Oamentioning

confidence: 99%

The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

2016

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MicroRNAs (miRNAs) are small, non-coding RNA species that are highly evolutionarily conserved, from higher invertebrates to man. Up to 1000 miRNAs have been identified in human cells thus far, where they are key regulators of the expression of numerous targets at the post-transcriptional level. They are implicated in various processes, including cell differentiation, metabolism, and inflammation. An expanding list of miRNAs is known to be involved in the pathogenesis of common, non-autoimmune inflammatory diseases. Interestingly, osteoarthritis (OA) is now being conceptualized as a metabolic disease, as there is a correlation among hyperuricemia and metabolic syndrome (MetS). Experimental evidence suggests that metabolic deregulation is a commonality between these different pathological entities, and that miRNAs are key players in the modulation of metabolic routes. In light of these findings, this review discusses the role of miRNAs in OA and gouty arthritis, as well as the possible therapeutic targetability of miRNAs in these diseases.

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Integrated Study of Globally Expressed microRNAs in IL-1β-stimulated Human Osteoarthritis Chondrocytes and Osteoarthritis Relevant Genes: A Microarray and Bioinformatics Analysis

Cited by 25 publications

References 26 publications

NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

Inhibition of microRNA‐27b‐3p relieves osteoarthritis pain via regulation of KDM4B‐dependent DLX5

The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

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