| Popis: |
This study aimed to explore the role of p53/p21 in osteoarthritis (OA). OA animal model was established by the anterior cruciate ligamentotomy (ACLT). 24 rats were randomly divided into control, OA, OA+p53 inhibitor and OA+pyroptosis inducer groups (n = 6). In the knee joint tissue, microstructural changes were analysed by Micro-CT. Histopathological changes were stained by HE and safranin-fast green. NLRP3 and Caspase-1 were detected by immunohistochemistry. The chondrocytes C-28I2 were divided into control, LPS+ ATP and p53 inhibitor groups. The cell viability, apoptosis, and LDH release were measured by MTT assay, TUNEL staining and LDH kit. The expression of p53/p21 and pyroptosis pathways were examined by western blot. The p53 inhibitor reduced the relative volume of trabecular bone (BV/TV) and trabecular bone thickness (Tb.Th), while increased trabecular separation (Tb.Sp). Moreover, the p53 inhibitor improved histopathological changes in the knee joint, attenuated cartilage damage, and reduced the expression of p53/p21 and pyroptosis pathways-related proteins. In vitro assay showed that the p53 inhibitor increased C-28I2 cell activity, reduced LDH release and apoptosis and reduced p53/p21 and pyroptosis pathways-related proteins. Totally, p53 inhibitors improved the cartilage tissue and chondrocyte damage, inhibited cell pyroptosis and the progression of OA. |
