Abstract
Objective To evaluate the therapeutic effects of cross linked sodium hyaluronate acid(JZC11) on experimentally induced osteoarthritic changes in rabbit knee joint and its protective roles on OA patients cartilage in vitro.Methods Osteoarthritis(OA) rabbits were established by the classic Hulth method The study groups was intra-articular injected with JZC11(1.3,2.1,2.9mg/kg,0.8ml,once) in one joint of model rabbit,and hyaluronate acid(HA,1.3mg/kg,once a week for 5 weeks)as a control was intra-articular injected in one joint,too. In addition,the sham operation animals and model animals was delivered with the same volume of saline.Animals were sacrificed at 6 weeks after first administration.The perimeter difference value between the two joints of rabbits was detected and histological changes in articular cartilage,osteochondral junction,chondrocyte appearance and subchondral bone were determined,MMP3 and TIMP1 expression were detcted by immunohistochemical staining.To observe the effect of JZC11 on OA patients cartilage and chondrocyte in vitro,Glycosaminoglycan in cartilage explants and cytokines in cells cultural supernatant were detected.Results Regarding perimeter difference value and knee joint Pelletier score,there were a statistically significant difference between JZC11(2.1,2.9mg/kg)groups and OA model rabbit.JZC11(2.1,2.9mg/kg)could decrease Mankins score and improve the joint pathology.Specially,JZC11(2.1mg/kg)could significantly reduce the knee joint X-ray score and increase the cartilage thickness.JZC11(2.1,2.9mg/kg)could also reduce the expression of MMP3 and increase the expression of TIMP1 in the joint cartilage.In vitro,JZC11 could significantly increase the GAG content of OA patients cartilage which lossed by IL-1beta induced degradation,and increase TIMP1 levels and restore the MMP3/TIMP1 ratio in OA patients chondrocytes.Conclusion Intra-articular injection of JZC11 had an obvious therapeutic effects on rabbit knee osteoarthritis,which could improve the joint pathology,alleviate cartilage degradation and restore the balance of MMPs and TIMPs.
