Study on the Correlation between Biological Clock and Cell Cycle in Knee Osteoarthritis Cartilage
Objective:The purpose of this study is to investigate the expression difference,correlation and function of circadian clock and cell cycle related genes in knee osteoarthritis(KOA)and normal cartilage.Methods:Sixty patients with KOA who underwent knee arthroplasty were selected.The tibial plateau and medial and lateral femoral condyle cartilage were collected after operation.The ar-ticular cartilage with obvious damage and normal macroscopic observation was divided into osteoarthritis group(OA group)and relatively normal group(Normal group).HE and safranine fast green staining were used to observe the pathological changes of cartilage tissue.The mRNA expression levels of BMAL1,PER1,CDK1,CCNB1 and MMP13 were detected by reverse transcription polymerase chain reac-tion(RT-PCR).The expression differences between OA group and Normal group were analyzed,and the correlation between them was analyzed.The expression levels of BMAL1,PER1,CDK1,CCNB1 and MMP13 proteins were detected by immunohistochemistry and Western blotting,and their expression differences between OA group and Normal group were further verified.Results:Compared with the Normal group,the cartilage surface of the OA group was not smooth,the cartilage became thinner,the matrix was destroyed,the pro-teoglycan was significantly lost,and the cartilage thickness was reduced.The expression of BMAL1 in OA group decreased,and the mR-NA expression and protein expression levels of CDK1,CCNB1,PER1 and MMP13 increased significantly(P<0.05).Correlation analysis showed that BMAL1 was negatively correlated with CDK1,CCNB1,PER1 and MMP13,and there was a positive correlation between CDK1,CCNB1,PER1 and MMP13.Conclusion:There is a coupling relationship between clock and cell cycle in knee cartilage,and there is a difference in expression between KOA cartilage and normal cartilage.BMAL1 may be a protective factor for KOA,and CDK1,CCNB1,PER1 and MMP13 may be risk factors.