Abstract:

Objective    To compare the different effects of aggrecanases and MMPs by detecting the expression of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3 proteins in the synovial fluid (SF) of patients with different stages of osteoarthritis (OA).  Methods   A total of 144 patients with knee OA were studied and the patients were divided into early-, middle- and late-stage OA groups according to the degree of knee articular cartilage degeneration which was assessed by Recht′s grading standard of MRI image and Outerbridge grading standard under arthroscope. Expressions of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, ARGxx and FFGxx in the SF were investigated and compared by enzyme-linked immunosorbent assay and Western blot. Results   Both ADAMTS-4 and ADAMTS-5 had higher expressions in the early- and late-stage OA groups than those in the middle-stage group, while the expression of ADAMTS-4 in the early-stage OA group was significantly higher than that in the late-stage OA group(P<0.01). Compared with the middle-stage OA group, MMP-1 had higher expression in the late-stage OA group and MMP-3 had higher expression in the early-stage OA group (P<0.05). ARGxx had a significantly higher level in the earlystage OA group (P<0.01). Conversely, FFGxx had higher expression in the late-stage group than those in the early-  and middle-stage groups (P<0.01). The expression levels of ADAMTS-5, MMP-3 and ARGxx in the three groups were significantly higher than those of ADAMTS-4, MMP-1 and FFGxx respectively (P<0.01). Both ADAMTS-4 and -5 expressions were positively correlated with ARGxx (P<0.01), and the expression of ADAMTS-4 was more closely related to it (r=0.530 vs r=0.285). Western blot analysis revealed the expression of ADAMTS-4 significantly increased in the early-stage group (P<0.05), while ADAMTS5 had higher expression in both early-stage and late-stage groups (P<0.05). MMP-1 and FFGxx had higher expression in the late-stage group (P<0.05), while MMP-3 was higher in the early-stage group than in the middle-stage group (P<0.05). Besides, the expressions of ARGxx in early- and latestage OA groups were significantly higher than that in the middle-stage group (P<0.05). Conclusion   Aggrecanases are primarily involved in the cartilage destruction in the early and late stages of OA, however, matrix metalloproteinases mainly performed in the late stage of OA in human.