“…Recently, increasing evidences demonstrated that lncRNAs are key elements of pathologic and physiologic processes, and are vital regulators of inflammatory response [9, 10]. Previous study reported that cartilage injury-related lncRNA (lncRNA-CIR) was higher expressed in chondrocytes induced by interleukin-1(IL-1), and inhibited the formation of collagen and aggrecan in OA [11].…”
Background/Aims: Several long non-coding RNAs (lncRNAs) play vital roles in osteoarthritis (OA), whereas the role of lncRNA RP11-445H22.4 in OA remains unclear. The study aimed to investigate the effect of lncRNA RP11-445H22.4 on lipopolysaccharide (LPS)-induced cell viability, apoptosis and inflammatory injury of OA. Methods: The expression of RP11-445H22.4, miR-301a and CXCR4 in human cartilage ATDC5 cells were altered by transfection, and then cells were exposed to 5 µg/ml LPS for 12 h. Then cell viability, apoptosis, apoptosis-related factors and inflammatory cytokines were analyzed by CCK-8, flow cytometry, western blot, RT-qPCR and ELISA, respectively. Dual-luciferase reporter assay was performed to assess the binging sites of RP11-445H22.4 and miR-301a. The signal pathways of NF-κB and MAPK/ ERK were determined by western blot. Results: LPS reduced cell viability, increased apoptosis and stimulated release of IL-1β, IL-6, IL-8 and TNF-α. However, RP11-445H22.4 inhibition significantly rescued LPS-induced injuries by promoting cell viability, suppressing apoptosis and inflammatory cytokines secretions in ATDC5 cells. In addition, miR-301a directly bound to RP11-445H22.4, and suppression of miR-301a inversed the effects of RP11-445H22.4 inhibition. Furthermore, CXCR4 was a direct target of miR-301a, and CXCR4 silencing increased cell viability, decreased apoptosis and inflammatory cytokines secretions in LPS-treated ATDC5 cells. Besides, we found that CXCR4 silencing blocked LPS-activated NF-κB and MAPK/ERK pathways. Conclusions: The study indicated that lncRNA RP11-445H22.4-miR-301a-CXCR4 axis played an important role in cartilage ATDC5 cells and provided a theoretical basis of lncRNA RP11-445H22.4 in OA.
“…Recently, increasing evidences demonstrated that lncRNAs are key elements of pathologic and physiologic processes, and are vital regulators of inflammatory response [9, 10]. Previous study reported that cartilage injury-related lncRNA (lncRNA-CIR) was higher expressed in chondrocytes induced by interleukin-1(IL-1), and inhibited the formation of collagen and aggrecan in OA [11].…”
Background/Aims: Several long non-coding RNAs (lncRNAs) play vital roles in osteoarthritis (OA), whereas the role of lncRNA RP11-445H22.4 in OA remains unclear. The study aimed to investigate the effect of lncRNA RP11-445H22.4 on lipopolysaccharide (LPS)-induced cell viability, apoptosis and inflammatory injury of OA. Methods: The expression of RP11-445H22.4, miR-301a and CXCR4 in human cartilage ATDC5 cells were altered by transfection, and then cells were exposed to 5 µg/ml LPS for 12 h. Then cell viability, apoptosis, apoptosis-related factors and inflammatory cytokines were analyzed by CCK-8, flow cytometry, western blot, RT-qPCR and ELISA, respectively. Dual-luciferase reporter assay was performed to assess the binging sites of RP11-445H22.4 and miR-301a. The signal pathways of NF-κB and MAPK/ ERK were determined by western blot. Results: LPS reduced cell viability, increased apoptosis and stimulated release of IL-1β, IL-6, IL-8 and TNF-α. However, RP11-445H22.4 inhibition significantly rescued LPS-induced injuries by promoting cell viability, suppressing apoptosis and inflammatory cytokines secretions in ATDC5 cells. In addition, miR-301a directly bound to RP11-445H22.4, and suppression of miR-301a inversed the effects of RP11-445H22.4 inhibition. Furthermore, CXCR4 was a direct target of miR-301a, and CXCR4 silencing increased cell viability, decreased apoptosis and inflammatory cytokines secretions in LPS-treated ATDC5 cells. Besides, we found that CXCR4 silencing blocked LPS-activated NF-κB and MAPK/ERK pathways. Conclusions: The study indicated that lncRNA RP11-445H22.4-miR-301a-CXCR4 axis played an important role in cartilage ATDC5 cells and provided a theoretical basis of lncRNA RP11-445H22.4 in OA.
“…LncRNAs, a type of noncoding RNAs, could regulate gene expression via transcription, translation, and epigenetic modifications of DNA (Pearson & Jones, ). Some studies have provided convincing evidence that lncRNAs, rich in mammalian transcriptomes, exert a critical role in various biological processes including differentiation and development, and also leading to diseases when they are misregulated (Dey et al, ; Johnsson, Lipovich, Grander, & Morris, ).…”
Section: Introductionmentioning
confidence: 99%
“…Some studies have provided convincing evidence that lncRNAs, rich in mammalian transcriptomes, exert a critical role in various biological processes including differentiation and development, and also leading to diseases when they are misregulated (Dey et al, ; Johnsson, Lipovich, Grander, & Morris, ). Notably, it has been indicated that lncRNAs could modulate pathologic and physiologic processes, and may involve in the inflammatory response or inflammatory pathways in rheumatoid arthritis (RA) and OA (Pearson & Jones, ). It has been known that lncRNA LOC101928134 is located in the region of chromosome 15q13.3 according to databases.…”
Osteoarthritis (OA) is the most common disease of arthritis, a chronic joint disease that is always correlated with massive destruction such as cartilage destruction, inflammation of the synovial membrane, and so on. This study aims to explore the role of long noncoding RNA (lncRNA) LOC101928134 in the synovial hyperplasia and cartilage destruction, more specifically, in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in an OA rat model. Microarray‐based gene expression analysis was conducted to screen out the lncRNA differentially expressed in OA and predict the target gene of the lncRNA with the involvement of the signaling pathway through Kyoto encyclopedia of genes and genomes (KEGG) analysis. A model of OA was established and treated with the small interfering RNA LOC101928134/inhibitor of JAK/STAT signaling pathway to investigate the relationship among LOC101928134, IFNA1, and the JAK/STAT signaling pathway in OA. The effect of LOC101928134 on the serum levels of IFNA1, interleukin‐1β, and tumor necrosis factor‐α, and the apoptosis of synovial and cartilage cells was evaluated. LOC101928134, which was found to be highly expressed in knee joint synovial tissues of OA rats, regulated the expression of IFNA1 gene and inhibited JAK/STAT signaling pathway. Downregulation of LOC101928134 resulted in reduced knee joint synovitis, relived inflammatory damage, and knee joint cartilage damage of OA rats. Besides, synovial cell apoptosis was enhanced upon LOC101928134 downregulation, while cartilage cell apoptosis of OA rats was suppressed. These results demonstrate that downregulation of LOC101928134 suppresses the synovial hyperplasia and cartilage destruction of OA rats via activation of JAK/STAT signaling pathway by upregulating IFNA1, providing a new candidate for the treatment of OA.
“…1 Despite many decades of research, the pathogenesis underlying RA remains largely unknown, although several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL- 6), have been reported to contribute to the RA development. 1 Despite many decades of research, the pathogenesis underlying RA remains largely unknown, although several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL- 6), have been reported to contribute to the RA development.…”
Section: Introductionmentioning
confidence: 99%
“…1 Despite many decades of research, the pathogenesis underlying RA remains largely unknown, although several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL- 6), have been reported to contribute to the RA development. [4][5][6][7] Moreover, lncRNAs have been shown to play varied critical roles including inhibition of transcriptional machinery, affecting mRNA stability, regulating epigenetic DNA modifications, enhancing RNA degradation, and directing the apoptosis of different immune cells, in a variety of biological and cellular processes. Several studies have found that lncRNAs could be significant regulatory factors to inflammatory gene expression in innate immune system and play important roles in multiple autoimmune diseases.…”
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