The Protective Mechanism of SIRT1 on Cartilage Through Regulation of LEF-1

Abstract Background: Osteoarthritis as a chronic degenerative disease suppresses middle-aged and elderly people all over the world. In this study, we found the expression changes of lymphocyte enhancer factor 1 (LEF-1) from human specimens, and then found the regulatory relationship between silent information regulator 1（SIRT-1） and LEF-1 during osteoarthritis development and its effect on cartilage protection. Material/Methods: First, changes in the expression of LEF-1 protein were found in fresh specimens of the tibial plateau of patients with osteoarthritis, and then the hypothesis was verified mice model. Mice were randomly divided into three groups, including the normal group, model building, and drug spraying group. Each group is divided into two periods: 2 weeks after modeling and 8 weeks after modeling. Histological staining, immunohistochemistry, immunofluorescence, and qPCR experiments were used to detect the expression of SIRT-1, β-catenin, LEF-1, matrix metalloproteinase 13(MMP-13) and Collagen II.Result: LEF-1 increased with the severity of osteoarthritis in human specimens. We observed in animals: when osteoarthritis symptoms worsened, the expression of SIRT-1 and Collagen II gradually decreased, the expression of β-catenin, LEF-1, and MMP-13 and cartilage destruction gradually increased. Conclusion: Sirt-1 plays a protective role in cartilage by reducing the expression of β - Catenin, LEF-1 and MMP-13, and increasing the expression of collagen II.