金雀异黄酮对依托泊苷诱导软骨细胞衰老的保护作用及其机制OA

Objective To investigate the protective effect of genistein(Gen)on etoposide-induced chondrocyte se-nescence and its underlying mechanism.Methods The C28/I2 cell line was treated with different concentrations of Gen and etoposide,and the cell viability was detected by the CCK-8 assay.The senescence model of C28/I2 chondrocytes was induced by etoposide,with Gen intervention.Senescence-associated β-galactosidase(SA-β-gal)staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes.The ex-pressions of peroxiredoxin 6(Prdx6),cyclin-dependent kinaseto clarify the functional necessity of Prdx6.Results Compared with the etoposide group,the C28/I2 chondrocyte viability significantly increased(P<0.01),the expres-sion ofsenescence-associated proteins p21 and p16 decreased(P<0.01,P<0.05),the expression of senescence-associated genes p21 and p16 reduced(both P<0.01),the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished(P<0.05,P<0.01),and the proportion of SA-β-gal-positive cells decreased(P<0.01)in the Gen+etoposide group.Compared with the Control group,the expression of Prdx6 was downregulated in the etoposide group(P<0.05).Compared with the etoposide group,the expression of Prdx6 was upregulated in the Gen+etoposide group(P<0.01).Compared with the Control group,the GPx activity significantly decreased in the si-Prdx6 group(P<0.01).Furthermore,compared with the si-Prdx6 group,the GPx activity increased in the si-Prdx6+Gen group(P<0.05).Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6.After Prdx6 knockdown,the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group(both P<0.01).Conclusion Gen can inhibit etoposide-induced senescence of C28/I2 chondro-cytes by upregulating the expression of Prdx6.This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.