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  • Title: Downregulation of lncRNA SNHG14 attenuates osteoarthritis by inhibiting FSTL-1 mediated NLRP3 and TLR4/NF-κB pathway through miR-124-3p.
    Author: Wang B, Li J, Tian F.
    Journal: Life Sci; 2021 Apr 01; 270():119143. PubMed ID: 33539913.
    Abstract:
    Osteoarthritis (OA) is the joint pain and dysfunction syndrome caused by severe joint degeneration. The overproduced inflammatory mediators contribute greatly to OA development. It is reported that long non-coding RNA (lncRNA) takes part in many inflammatory diseases. Here, we mainly explored the function of lncRNA SNHG14 in OA process and its specific mechanisms. An OA rat model was induced by destabilizing the medial meniscus (DMM) and IL-1β (5 ng/mL) was used to mediate an OA cell model in particular chondrocytes (AC). Gain- or loss-of functional assays of SNHG14 and miR-124-3p were carried out to explore their roles in OA development. The experimental statistics illustrated that lncRNA SNHG14 and IL-1β mRNA expression were both increased in OA tissues, while miR-124-3p was lowly-expressed. Linear regression analysis showed that SNHG14 and miR-124-3p had negative relationship in the OA tissues. In the in vitro experiments, downregulation of lncRNA SNHG14 promoted the proliferation of IL-1β-treated AC and inhibited cell apoptosis and COX-2, iNOS, TNF-α, IL-6 expression. Moreover, lncRNA SNHG14 inhibited miR-124-3p expression as a miRNA sponge. MiR-124-3p targeted the 3'non-translated region (3'UTR) of FSTL-1 and TLR4 and inhibited their expressions. Also, the in vivo experiments confirmed that knocking down SNHG14 relieved the progression of OA in rats via inhibiting inflammatory responses. In conclusion, this study confirmed that downregulation of lncRNA SNHG14 inhibits FSTL-1-mediated activation of NLRP3 and TLR4/NF-κB signalling pathway activation by targeting miR-124-3p, thus attenuating inflammatory reactions in OA.
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