LncRNA GAS5 Overexpression Reverses LPS-Induced Inflammatory Injury and Apoptosis Through Up-Regulating KLF2 Expression in ATDC5 Chondrocytes

摘要

Background/Aims Osteoarthritis (OA) is the most frequently occurring joint disease and characterized by degeneration of cartilage. As the unique cell type in cartilage, chondrocytes play a crucial role during OA. Our study explored the influence of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on lipopolysaccharides (LPS)-induced injury in ATDC5 cells. Methods Cell viability, apoptosis and expression of inflammatory cytokines were all assessed to evaluate LPS-induce inflammatory injury. Expression of GAS5 in LPS-induced cells was evaluated by qRT-PCR. After cell transfection, effect of abnormally expressed GAS5 on LPS-induced inflammatory injury was determined. Then, the possible target of GAS5 was screened by bioinformatics and verified by qRT-PCR and luciferase activity assay. Together, whether aberrant expression of target gene affected the modulation of GAS5 in LPS-induced inflammatory injury was also assessed. Finally, the influences of aberrant expressed Kruppel-like factor 2 (KLF2) on nuclear factor κB (NF-κB) and Notch pathways were detected by Western blot analysis. Results LPS reduced cell viability and promoted cell apoptosis and secretion of inflammatory cytokines, along with down-regulation of GAS5. LPS-induced injury was alleviated by GAS5 overexpression while was exacerbated by GAS5 silence. KLF2 was predicted and verified as a target of GAS5, and GAS5 functioned through regulating expression of KLF2. Besides, aberrant expression of KLF2 regulated expressions of key kinases involved in the NF-κB and Notch pathways. Conclusion GAS5 might ameliorate LPS-induced inflammatory injury in ATDC5 chondrocytes by inhibiting the NF-κB and Notch signaling pathways.