Studying microRNAs in osteoarthritis: Critical overview of different analytical approaches

Trachana, Varvara; Ntoumou, Eleni; Anastasopoulou, Lydia; Tsezou, Aspasia

doi:10.1016/j.mad.2018.02.006

Cited by 26 publications

(26 citation statements)

References 88 publications

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“…folds (24,25). Increasing evidence has suggested that a number of miRNAs are associated with OA progression (26); therefore, the role of miRNAs in chondrocyte apoptosis and ECM degradation was investigated in the present study.…”

Section: Discussionmentioning

confidence: 93%

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Yuan

Song

et al. 2020

Exp Ther Med

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Osteoarthritis (OA) is a joint disease caused by a variety of factors, including aging, obesity and trauma. MicroRNAs (miRNAs) have been reported to be crucial regulators during OA progression. The present study aimed to investigate the role of miR-17-5p and miR-19b-3p during OA development. Interleukin (IL)-1β-treated chondrocytes were used to mimic OA in vitro. The expression levels of miR-17-5p and enhancer of zeste homolog 2 (EZH2) were measured in cartilage tissues and chondrocytes using reverse transcription-quantitative PCR or western blotting. Apoptosis was assessed by flow cytometry. The protein expression levels of extracellular matrix (ECM)-associated genes were detected by western blotting. The binding sites between miR-17-5p or miR-19b-3p and EZH2 were predicted using the MicroT-CDS online database and verified using dual-luciferase reporter and RIP assays. miR-17-5p expression was downregulated, whereas EZH2 expression was upregulated in OA cartilage tissues and IL-1β-induced chondrocytes compared with that in the control tissues and cells. miR-17-5p mimics inhibited IL-1β-induced apoptosis and ECM degradation in chondrocytes. EZH2 was the target of miR-17-5p and miR-19b-3p in chondrocytes, and enhanced apoptosis and ECM degradation in IL-1β-stimulated chondrocytes. Rescue experiments revealed that miR-17-5p or miR-19b-3p mimic-induced inhibition of OA progression was reversed by EZH2 overexpression. In conclusion, miR-17-5p and miR-19b-3p inhibited OA progression by targeting EZH2, which may serve as a potential therapeutic target for OA.

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Section: Discussionmentioning

confidence: 93%

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Yuan

Song

et al. 2020

Exp Ther Med

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“…miR‐140 is downregulated in OA cartilage and the intra‐articular injection of miRNA‐140 alleviates OA progression in rats . The potential role of other miRNAs in OA pathogenesis has been recently reviewed . In a few cases, their effects have been validated by gain‐of‐function or loss‐of‐function experiments in vivo (Table ).…”

Section: Non‐coding Rnas In Skeletal Disordersmentioning

confidence: 99%

“…Many cells can secrete miRNAs (mainly via exosomes) that are detectable in the synovial fluid and the circulation. Hence, several miRNAs have been suggested as potential biomarkers for the diagnosis or follow‐up of skeletal disorders (see recent reviews) . However, in general, the identity of regulated miRNAs varies widely across the studies and sometimes conflicting evidence is found.…”

Section: Non‐coding Rnas In Skeletal Disordersmentioning

confidence: 99%

Role of Epigenomics in Bone and Cartilage Disease

Meurs

Boer

López-Delgado

et al. 2019

Journal of Bone and Mineral Research

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Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors, other than DNA sequence, that cause stable changes in gene expression and are maintained during cell divisions. They represent a link between environmental influences, genome features, and the resulting phenotype. The main epigenetic factors are DNA methylation, posttranslational changes of histones, and higher-order chromatin structure. Sometimes non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are also included in the broad term of epigenetic factors. There is rapidly expanding experimental evidence for a role of epigenetic factors in the differentiation of bone cells and the pathogenesis of skeletal disorders, such as osteoporosis and osteoarthritis. However, different from genetic factors, epigenetic signatures are cell-and tissue-specific and can change with time. Thus, elucidating their role has particular difficulties, especially in human studies. Nevertheless, epigenomewide association studies are beginning to disclose some disease-specific patterns that help to understand skeletal cell biology and may lead to development of new epigenetic-based biomarkers, as well as new drug targets useful for treating diffuse and localized disorders. Here we provide an overview and update of recent advances on the role of epigenomics in bone and cartilage diseases.Besides chromatin-related marks and structure, non-coding RNAs (ncRNAs) are also frequently included among the mechanisms of epigenetic control. (8) They are classified as small RNAs (<200 nucleotides) and long RNAs (>200 nucleotides). The best-known subset of small RNAs are microRNAs (miRNAs, 18 to 25 nucleotides), which inhibit protein synthesis by binding to the 3 0 -untranslated region of target mRNAs. Long non-coding RNAs (lncRNAs) modulate the activity of both nearby genes and distant genes by a variety of mechanisms. For instance, they often serve as scaffolds for transcription factors and other molecules involved in initiation of transcription, including Box 1. Epigenomics-Related TermsChromatin: The complex of DNA and its packaging molecules. The core of the chromatin is the nucleosome, which consists of an octamer of 4 histones around which 147 bp of DNA is wrapped around.Chromosome conformation capture and Hi-C: Techniques used to map the spatial (3D) organization of the chromatin in the nucleus. Chromosome conformation capture (3C) quantifies the number of interactions between a given loci and the rest of the genome. In Hi-C, all genomic interaction between all genomic regions are quantified.CTCF: CCCTC-binding factor, highly conserved zinc finger protein involved in diverse genomic regulatory functions, including transcriptional activation/repression, insulation, imprinting, and X-chromosome inactivation, through mediating the formation of chromatin loops. DNA methyl-transferases (DNMTs): Family of enzymes responsible for the methylation of DNA. DNMT1...

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“…microRNAs (miRNAs) are single-stranded RNA molecules that are widespread presented in eukaryotes, containing about 17 to 25 nucleotides. During OA, many miRNAs are expressed abnormally, and thus miRNAs present in human plasma and synovial fluid have been considered as promising biomarkers for OA [5]. For instance, the expressions of miR-483, miR-22, and miR-377 were elevated, and miR-140, miR-29a and miR-25 were downregulated in OA chondrocytes [6].…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of MiR-150 Alleviates Inflammatory Injury Induced by Interleukin 1 via Targeting Kruppel-Like Factor 2 in Human Chondrogenic Cells

Yang

Zhang

Gao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Interleukin-1 (IL-1) is known to be involved in cartilage degeneration following joint injury or due to osteoarthritis. In the present study, we explored the effects of miR-150 on IL-1-stimulated human chondrogenic cells ATDC5. Methods: ATDC5 cells were transfected with the mimic, inhibitor or negative controls specific for miR-150, and subsequently treated by IL-1. CCK8 assay, PI and FITC-conjugated Annexin V double-staining, Western blot, qRT-PCR and ELISA assay were performed to determine the changes of cell viability, apoptosis, and the release of pro-inflammatory cytokines. Targeting relationship between miR-150 and KLF2 was detected by dual luciferase activity assay. Results: IL-1 reduced cell viability, induced apoptosis, and enhanced the expression and release of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) in ATDC5 cells. IL-1 also increased the expression of miR-150. Suppression of miR-150 alleviated IL-1-induced cell damage in ATDC5 cells, while overexpression of miR-150 resulted in an opposite impact. KLF2 was negatively regulated by miR-150, and it was proved as a target gene of miR-150. KLF2 overexpression exhibited protective actions in IL-1-injured ATDC5 cells, even if miR-150 was suppressed in cell. Moreover, IL-1-induced activation of NF-kB and Notch pathways was alleviated by KLF2 overexpression. Conclusions: Suppression of miR-150 led to up-regulation of KLF2, which in turn protected ATDC5 cells against IL-1-induced injury.

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Studying microRNAs in osteoarthritis: Critical overview of different analytical approaches

Cited by 26 publications

References 88 publications

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Role of Epigenomics in Bone and Cartilage Disease

Down-Regulation of MiR-150 Alleviates Inflammatory Injury Induced by Interleukin 1 via Targeting Kruppel-Like Factor 2 in Human Chondrogenic Cells

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