Downregulation of lncRNA SNHG14 attenuates osteoarthritis by inhibiting FSTL-1 mediated NLRP3 and TLR4/NF-κB pathway through miR-124-3p.

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.

Wang B ，Li J ，Tian F 《-》

LncRNA SNHG7 alleviates IL-1β-induced osteoarthritis by inhibiting miR-214-5p-mediated PPARGC1B signaling pathways.

Xu J ，Pei Y ，Lu J ，Liang X ，Li Y ，Wang J ，Zhang Y ... -  《-》

Inhibition of long non-coding RNA HOXA11-AS against neuroinflammation in Parkinson's disease model via targeting miR-124-3p mediated FSTL1/NF-κB axis.

Cao H ，Han X ，Jia Y ，Zhang B ... -  《-》

[miR-515-5p targeting Toll-like receptor 4 regulates myeloid differentiation primary response gene 88/nuclear factor-kappa B pathway to inhibit apoptosis and inflammatory response of osteoarthritis chondrocytes].

Cai D ，Yang Z ，Zhong C ，Zhang J ，Hong S ... -  《-》

miR-382-3p suppressed IL-1β induced inflammatory response of chondrocytes via the TLR4/MyD88/NF-κB signaling pathway by directly targeting CX43.

miR-382-3p has been reported to be upregulated in synovial membrane in knee osteoarthritis (OA). Nevertheless, its role in OA remains largely unknown. The aim of this study was to investigate the specific function and mechanisms of miR-382-3p in the course of OA. In this study, human OA chondrocytes were pretreated with interleukin-1β (IL-1β) at 5 ng/ml for 12 hr to stimulate inflammatory response and matrix metalloproteinases (MMPs) expression in chondrocytes. Meanwhile, miR-382-3p was downregulated in IL-1β-stimulated chondrocytes. In addition, we found that miR-382-3p directly interacts with connexin 43 (CX43) and attenuates the increase of cytochrome c oxidase polypeptide II, inducible nitric oxide synthase, and MMP-1/13 that is induced by IL-1β. Furthermore, our observations indicated that miR-382-3p inhibited the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation primary response 88 (MyD88) and nuclear factor κB (NF-κB) in IL-1β-stimulated chondrocytes, while CX43 overexpression could partly reverse these decreases. In conclusion, miR-382-3p participated in OA may through the TLR4/MyD88/NF-κB signaling pathway by directly targeting CX43.

Lei J ，Fu Y ，Zhuang Y ，Zhang K ，Lu D ... -  《-》