Long noncoding RNAs (lncRNAs) participate in multiple diverse diseases, including osteoarthritis (OA). Here, we explored the role of lncRNA XIST in OA and identified the potential molecular mechanisms. The expression of XIST in cartilage samples in patients with OA was significantly upregulated. XIST knockdown remarkably suppressed IL-1 beta-suppressed OA chondrocyte proliferation while promoted IL-1 beta-induced cell apoptosis. By employing online tools, miRNAs related to CXCR4, a major contributor to chondrocyte apoptosis, and XIST were selected. miR-211 expression could be significantly inhibited by IL-1 beta stimulation, and miR-211 negatively regulated XIST expression and CXCR4 protein levels. Through direct binding, XIST served as a ceRNA for miR-211 to counteract miR-211-mediated CXCR4 repression, thereby modulating chondrocyte proliferation and apoptosis through downstream MAPK signaling. In OA tissues, miR-211 expression was significantly downregulated while CXCR4 mRNA expression was upregulated. miR-211 was negatively correlated with XIST and CXCR4, respectively, while XIST and CXCR4 was positively correlated in tissue samples. In conclusion, the study revealed that lncRNA XIST can promote the proliferation of OA chondrocytes and promote apoptosis through the miR-211/CXCR4 axis. Thus, lncRNA XIST might be considered as a potential therapeutic target for OA treatment. (C) 2018 Elsevier Inc. All rights reserved.