ObjectiveTo investigate the effect of inhibiting autotaxin (ATX)-lysophosphatidic acid (LPA) pathway on the cartilage of knee osteoarthritis in rats.MethodsPrimary chondrocytes within three generations of Sprague-Dawley rats (8 weeks old, male) were randomly divided into 6 groups, including blank control group, model group, 1 μmol/L PF-8380 group, 10 μmol/L PF-8380 group, 1 μmol/L Ki16425 group, and 10 μmol/L Ki16425 group. Except for the blank control group, the other groups were modeled with osteoarthritis using interleukin-1β (10 ng/mL, 24 h), and then the experimental groups, i.e., 1 μmol/L PF-8380 group, 10 μmol/L PF-8380 group, 1 μmol/L Ki16425 group, and 10 μmol/L Ki16425 group, were intervened with 1, 10 μmol/L PF-8380 (ATX inhibitor) and 1, 10 μmol/L Ki16425 (LPA receptor antagonist) for 24 h, respectively. immunocytochemistry staining was used to determine the expression of type Ⅱ collagen (Col Ⅱ) in cytoplasm, and Western Blot was used to determine the expression of ATX, LPA, and matrix metalloproteinase-13 (MMP-13) in chondrocytes.ResultsCompared with the blank control group, the average absorbance of Col Ⅱ in chondrocytes in the model group was significantly reduced (0.003 9±0.000 8 vs. 0.110 0± 0.009 0, P<0.05). The expression levels of ATX, LPA, and MMP-13 in chondrocytes in the model group, 1 μmol/L PF-8380 group, 10 μmol/L PF-8380 group, and 1 μmol/L Ki16425 group were significantly higher than those in the blank control group, while the expression levels of ATX, LPA, and MMP-13 in the 10 μmol/L Ki16425 group had no significant difference with those in the blank control group; the expression levels of ATX, LPA, and MMP-13 in the model group, 10 μmol/L PF-8380 group, and 1 μmol/L PF-8380 group decreased in order; the expression levels of ATX, LPA, and MMP-13 in the model group, 1 μmol/L Ki16425 group, and 10 μmol/L Ki16425 group decreased in order.ConclusionInhibiting ATX-LPA pathway may inhibit the up-regulation of MMP-13 levels in articular cartilage of osteoarthritis in rats to reduce the damage of cartilage.