Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders

To explore the levels of matrix metalloprotease-3 (MMP-3), tissue inhibitor of metalloproteases-1 (TIMP-1), 5D4 keratan sulfate, and two 3B3 chondroitin-sulfate epitopes in several canine osteoarthritic and inflammatory arthropathies.

Blood and synovial fluid were obtained from 103 dogs with rupture of the anterior cruciate ligament (ACLR), osteochondritis dissecans (OCD), fragmented coronoid process (FPC), patella luxation (PL), hip dysplasia (HD) or infectious arthritis. Dogs with non-musculosceletal disorders were used as controls. The biomarkers were measured by immunoassays.

Median levels of synovial MMP-3, TIMP-1 and molar ratios of MMP/TIMP-1 were significantly higher in the arthritis than in the control group. The release of 5D4 keratan sulfate epitope and serum 3B3 neoepitope was reduced in arthritis patients. Increases in synovial TIMP-1 in OA were less pronounced and the molar ratio of MMP-3/TIMP-1 remained far below 1.0, demonstrating a surplus of the protease inhibitor. In osteoarthritic patients median levels of synovial 5D4 keratan sulfate were up-regulated after ACLR and PL and were inversely correlated with increasing duration of lameness. Serum TIMP-1 levels were significantly reduced in the joint disorder group when compared with the control group.

Our observations present the TIMP-1 serum level as a potential marker for the detection of degenerative changes in cartilage and also indicate that in canine OA, the MMP-3 mediated matrix destruction is not of major importance. However MMP-3 seems to be a sensitive marker for the local inflammation in canine arthritis.