| Objective To investigate the effect of daphnetin (DAPH) on pyroptosis of chondrocytes in osteoarthritis (OA) rats by regulating the MCP-1/CCR2 signaling axis. Methods A rat model of osteoarthritis was established by removing the anterior cruciate ligament and medial meniscus, and was randomly separated into an OA group, a low-dose DAPH (DAPH-L, 30 mg/kg) group, a high-dose DAPH (DAPH-H, 90 mg/k) group, a DAPH-H+CCL2 (5 ng CCL2) group, and a celecoxib (20 mg/kg) group. Ten rats with only open joint cavities were used as the sham surgery group, imaging was applied to analyze bone density (BMD), trabecular bone number (Tb-N), and bone volume fraction (BV/TV); ELISA was applied to detect the levels of interleukin-1β (IL-1β) and IL-18 in the serum of each group; HE and safranin were applied to detect morphological changes in cartilage tissue; qRT-PCR was applied to detect gene expression related to cartilage tissue necrosis (ASC, NLRP3, Caspase-1); Western blot was applied to detect the expression of MCP-1 and CCR2 proteins in cartilage tissue. Results Compared with the sham surgery group, the BMD, Tb-N, BV/TV in the OA group were decreased, the levels of IL-1β and IL-18 in serum, and the expression of ASC, NLRP3, Caspase-1 mRNA, MCP-1, and CCR2 proteins in cartilage tissue were increased (P<0.05); compared with the OA group, the BMD, Tb-N, BV/TV in the DAPH-L group, DAPH-H group, and celecoxib group were increased, the levels of IL-1β and IL-18 in serum, and the expression of ASC, NLRP3, Caspase-1 mRNA, MCP-1, and CCR2 proteins in cartilage tissue were reduced, and there was a statistically obvious difference between the DAPH-L group with the DAPH-H group and the celecoxib group, respectively (P<0.05), but there was no statistically obvious difference between the DAPH-H group and the celecoxib group (P>0.05); compared with the DAPH-H group, the BMD, Tb-N, BV/TV in the DAPH-H+CCL2 group were decreased, the levels of IL-1β and IL-18 in serum, and the expression of ASC, NLRP3, Caspase-1 mRNA, MCP-1, and CCR2 proteins in cartilage tissue were increased (P<0.05). Conclusion DAPH reduces pyroptosis of chondrocytes in OA rats by regulating the MCP-1/CCR2 signaling axis. |