| Objective To investigate the regulatory mechanism of lncRNA X inactive specific transcript (XIST) on interleukin-1β (IL-1β)-induced chondrocyte injury by targeting miR-302a-3p. Methods The human chondrosarcoma cell line SW1353 in vitro was induced by 10 ng/mL IL-1β to simulate osteoarthritis (OA)-like chondrocyte injury. SW1353 cells were separated into Control group, IL-1β group, IL-1β+si-NC group, IL-1β+si-XIST group, IL-1β+si-PDK1 group, IL-1β+si-XIST+miR-NC inhibitor group, IL-1β+si-XIST+miR-302a-3p inhibitor group. To measure the expression of XIST, miR-302a-3p and 3-phosphoinositide-dependent protein kinase 1 (PDK1) mRNA; methyl thiazolyl tetrazolium (MTT) experiment was performed to determine the viability of cells; flow cytometry was performed to determine cell apoptosis; qRT-PCR was performed to determine the expression levels of inflammatory factors (TNF-α, IL-1β, IL-4, IL-6, IL-10); a dual-luciferase reporter gene assay was performed to confirm the targeting relationship of miR-302a-3p to XIST or PDK1; Western blot was performed to determine the expression of apoptotic protein (Bcl-2, Bax) and PDK1. Results Compared with IL-1β group, the expression of XIST in the IL-1β+si-XIST group was down-regulated, the cell viability was increased, the apoptosis rate was decreased, the expression of Bax and the levels of TNF-α, IL-1β and IL-6 was decreased, the expression of Bcl-2 and the levels of IL-4 and IL-10 was increased(P<0.05). XIST directly targeted and down-regulated the expression of miR-302a-3p, downregulation of miR-302a-3p was able to restore the pro-proliferative, anti-apoptotic and inflammatory responses mediated by si-XIST (P<0.05). PDK1 was a target gene of miR-302a-3p, the silencing of PDK1 inhibited the inflammatory response of cells (P<0.05). Conclusion Knockdown of XIST can improve the cell viability of IL-1β-induced chondrocytes, alleviate the damage of OA-like chondrocytes, and its mechanism is related to the inhibition of PDK1 expression by targeting the up-regulation of miR-302a-3p. |