microRNA‐138 induces cell survival and reduces WNT/β‐catenin signaling of osteoarthritis chondrocytes through NEK2

Xu, Weiling; Gao, Peihong; Zhang, Yan; Li, Piao; Dong, Dong

doi:10.1002/iub.2050

Cited by 25 publications

(16 citation statements)

References 43 publications

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“…We further hypothesize that the effect of mechanical loading or, specifically, of HP on Wnt/β-catenin pathway could be mediated by miRNA. Indeed, several investigations demonstrated, in human and rat OA chondrocyte cultures, the direct targeting of some miRNA, implicated in OA damage, on Wnt or β-catenin proteins [70][71][72][73]. Likewise, our data reported a reduced β-catenin protein expression when OA chondrocytes were transiently silenced with miR-34a specific inhibitor; moreover, miRNA inhibition limited the negative effects of overloading HP on β-catenin expression and enhanced, even if not significantly, those of low cyclic pressure.…”

Section: Discussionmentioning

confidence: 99%

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

Cheleschi

Barbarino

Gallo

et al. 2020

IJMS

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Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1–5 MPa) and continuous static HP (10 MPa) for 3~h. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and β-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. β-catenin protein expression was reduced in cells exposed to HP 1–5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/β-catenin pathway.

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Section: Discussionmentioning

confidence: 99%

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

Cheleschi

Barbarino

Gallo

et al. 2020

IJMS

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“…Numerous signaling pathways are involved in the process of OA, including bone morphogenetic proteins (8), Indian hedgehog (9), hypoxia-induced and Wnt signaling pathways (10,11). As an important component of the Wnt signaling pathway, β-catenin is activated by Wnt family proteins and participates in the pathological process of KOA (12).…”

Section: Introductionmentioning

confidence: 99%

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

et al. 2020

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Knee osteoarthritis (KOA) is a common joint disease with a high incidence rate among middle-aged and elderly individuals. However, the precise underlying pathological mechanisms and effective treatment of this disease remain to be determined. To explore the effect of high mobility group box 1 (HMGB1) on chondrocyte apoptosis and catabolism, the ATdc5 cell line was cultured as an in vitro model for cartilage research. cultured cells were treated with recombinant HMGB1 at different concentrations. Hoechst staining and flow cytometry demonstrated that HMGB1 administration significantly induced apoptosis of ATdc5 cells, which was the same as the effect of interleukin-1β treatment. HMGB1 also induced cartilage matrix degradation, as shown by Alcian blue staining. Moreover, HMGB1 markedly upregulated the expression levels of matrix metallopeptidases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (AdAMTS), while genetic silencing of HMGB1 significantly suppressed their expressions. The glycogen synthase kinase (GSK)-3β/β-catenin pathway was activated upon HMGB1 treatment. Pharmacological inhibitors or HMGB1 knockdown inactivated the GSK-3β/β-catenin pathway, inhibited the expression levels of downstream genes, including MMPs and AdAMTS, and attenuated the apoptosis of ATdc5 cells. Furthermore, the data demonstrated that HMGB1 promoted chondrocyte dysfunction via the regulation of estrogen sulfotransferase and Runt-related transcription factor 2. Thus, the findings of the present study demonstrated that HMGB1 induces chondrocyte cell apoptosis via activation of GSK-3β/β-catenin and the subsequent expression of multiple targeted genes.

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“…Numerous studies have shown that miRs are vital for maintaining cartilage homeostasis and developing cartilage destruction 14,15 . Evidence obtained in vivo and in vitro reveals that miR‐24, miR‐93‐5p and miR‐138 promote chondrocyte survival and attenuate cartilage degradation in OA via repressing their downstream targets 16–18 . Inversely, overexpression of miR‐495 may be linked with chondrocyte apoptosis by regulating chemokine ligand 4 in OA 14 .…”

Section: Introductionmentioning

confidence: 99%

miR‐877‐5p alleviates chondrocyte dysfunction in osteoarthritis models via repressing FOXM1

Zhu

Deng

Gao

et al. 2020

The Journal of Gene Medicine

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Background: The present study aimed to investigate whether forkhead box M1 (FOXM1), as a putative target of miR-877-5p, participated in interleukin (IL)-1βinduced cartilage degeneration in experimental osteoarthritis (OA) models in vitro and in vivo. Methods: In vitro and in vivo models of OA were established using IL-1β treated primary mouse chondrocytes and anterior cruciate ligament transection (ACLT) operation in mice. miR-877-5p mimics or agomir-miR-877-5p were used as therapeutic agents in both in vitro and in vivo models of OA. Cell viability and apoptosis were evaluated using cell counting kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining, respectively. A quantitative reverse transcriptasepolymerase chain reaction and western blotting were used to measure gene and protein expression, respectively. Results: FOXM1 was up-regulated in IL-1β-stimulated chondrocytes and the proximal tibia of ACLT-operated mice. Bioinformatics algorithms deduced a highly conserved sequence in the 3'-UTR of FOXM1 that could be bound with miR-877-5p. A luciferase assay indicated that miR-877-5p directly targeted the 3'-UTR of FOXM1. Overexpression of miR-877-5p could reduce protein expression of FOXM1 in chondrocytes. Concurrently, IL-1β-evoked up-regulation of FOXM1 protein expression was neutralized in chondrocytes following transfection with miR-877-5p mimics. miR-877-5p mimics or agomir-miR-887-5p could inhibit IL-1β-induced inflammation in both in vitro and in vivo models of OA. miR-877-5p might have beneficial effects on the synthesis of cartilage matrix via the promotion of SRY-box transcription factor 9 and type II collagen expression and inhibition of matrix metalloproteinase 9 expression. Conclusions: miR-877-5p can improve chondrocyte function in both in vivo and in vitro models of OA, based on post-transcriptional repression of FOXM1 as a postulated molecular mechanism.

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microRNA‐138 induces cell survival and reduces WNT/β‐catenin signaling of osteoarthritis chondrocytes through NEK2

Cited by 25 publications

References 43 publications

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

miR‐877‐5p alleviates chondrocyte dysfunction in osteoarthritis models via repressing FOXM1

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