〔Abstract〕 To explore the molecular mechanism of long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 ( MALAT1) /microRNA-15b-5p ( miR-15b-5p) regulating the Wnt/β-catenin path- way in lipopolysaccharide (LPS)-induced chondrocyte injury in osteoarthritis . Methods ATDC5 cells were treated with 5 mg/L LPS to establish the osteoarthritis cell injury model , and the expression levels of MALAT1 and miR- 15b-5p in the cells were detected by RT-qPCR . The MTT , flow cytometry , Alizarin red staining , and ELISA were used to assess the effects of MALAT1 and miR-15b-5p on LPS-induced chondrocyte injury . The dual-luciferase re- porter gene assay was used to examine the regulatory relationship between MALAT1 and miR-15b-5p . Western blot assay was used to evaluate the expression of relevant proteins . Results In LPS-induced ATDC5 cells , MALAT1 expression decreased (P < 0. 05) . Compared to the control group , the LPS group exhibited reduced cell activity , an increased apoptosis rate , elevated levels of tumor necrosis factor-α, interleukin-6 , and interleukin-1β, a higher number of calcified nodules , increased expression levels of extracellular matrix degradation-related proteins MMP13 and ADAMTS5 , decreased expression levels of Collagen Ⅱ and Aggrecan , and increased protein expression levels of Wnt1 and β-catenin (P < 0. 05) . Overexpression of MALAT1 could mitigate the effects of LPS on chondrocyte activity , apoptosis , inflammatory response , osteogenic differentiation , extracellular matrix degradation , and the Wnt/β-catenin pathway (P < 0. 05) . Additionally , the overexpression of miR-15b-5p enhanced the impact of LPS on chondrocytes (P < 0. 05) . Conclusion MALAT1 is lowly expressed in LPS-induced chondrocytes , and it alle- viates LPS-induced chondrocyte injury by targeting miR-15b-5p to inhibit the Wnt/β-catenin pathway .