Effect Of The Endothelin-1 On The Production Of Nitric Oxide And Matrix Metalloproteinases-1 By Rabbits Articular Chondrocytes Cultured In Vitro

Objective: Osteoarthritis(OA) was one of the most common diseases in the aging population.It was characterized by articular cartilage degradation and hypertrophic joint change and synovial membrane inflammation.Its pathogenesis was still unillustration.Cytokines and inflammatory mediators which broke the balance between synthesis and destructive metabolism played an important role in the pathogenesis of OA.The research was to study the influence of ET-1 in the production of NO and MMP-1 by rabbits articular chondrocytes cultured in vitro. TO study the role of ET-1 in OA pathogenesis.Methods: The rabbits articular chondrocytes which isolated from the two months age rabbits cultured in vitro.The second generation chondrocytes wose used and cultured in absence or presence of ET-1．then testing the concentration of NO and MMP-1 in the different concentration of ET-1 and the different times, the concentration of NO was measured by the ways of nitrate reductase , and PGE2 was measured by enzyme-linked immunosorbent assay(ELISA), and study the correlation between the groups by statistics analysis ways.Results: the concentrations of NO and MMP-1 in the groups that chondrocytes co-cultured with ET-1 were significantly higher than the groups that absentenc of ET-1(P<0．001) . the NO and MMP-1 production induced by ET-1 increased in dose-dependence marner.the productions of NO and MMP-1 were special relationships with the time of ET-1 co-cultured with chondrocytes.In the 24 hours,the concentrations of NO and MMP-1 were no significant difference between 12 hours and 24 hours. However, afer 24 hours,these concentrations were increased whit the cocultured time increased.Conclusion: 1．ET-1 could stimulate the rabbit chondrocytes to produce and release NO and MMP-1． 2．ET-1 took part in the injury of the cartilage by overproduction of NO and MMP-1 secreted by the chondrocytes. Blocking the effects of ET-1 may thus become a useful therapeutic approach aimed at stopping cartilage destruction in OA.