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  • Author or Editor: Bruce Caterson x
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Abstract

Objective—To investigate interglobular domain (IGD) cleavage of aggrecan in dogs with naturally developing osteoarthritis (OA).

Sample Population—Samples of synovial fluid (SF) obtained from 3 cubital (elbow) joints and 3 stifle joints of 4 clinically normal dogs, 24 elbow joints of 12 dogs with early-stage OA, 8 stifle joints of 5 dogs with early-stage OA, and 10 stifle joints of 9 dogs with latestage OA.

Procedure—Fractions of SF were assayed for total glycosaminoglycan (GAG) content and also subjected to western blot analysis by use of monoclonal antibodies against neoepitopes generated by cleavage of the IGD of the aggrecan protein core by matrix metalloproteinase (MMP; BC-14) and aggrecanase (BC-3).

Results—Total GAG content of SF from joints of clinically normal dogs did not differ from that of dogs with early-stage OA. The GAG content of SF from joints of dogs with late-stage OA was significantly lower, compared with GAG content for other SF samples. Aggrecanase-generated fragments were detected in SF from all groups but not in all samples. Matrix metalloproteinase– generated fragments were not detected in any SF samples. In early-stage OA, high-molecularweight aggrecanase-generated aggrecan catabolites were evident.

Conclusions and Clinical Relevance—GAG content of SF obtained from dogs with late-stage OA is significantly decreased, suggesting proteoglycan depletion of cartilage. Aggrecanases, but not MMPs, are the major proteolytic enzymes responsible for IGD cleavage of aggrecan in canine joints. Analyses of SF samples to detect aggrecanase-generated catabolites may provide an early biomarker for discriminating early- and latestage OA in dogs. (Am J Vet Res 2005;66:1679–1685)

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in American Journal of Veterinary Research

Abstract

Objective—To compare synovial fluid biomarkers of cartilage metabolism in joints with naturally acquired or experimentally induced cranial cruciate ligament (CCL) rupture and determine correlations with stage and severity of disease in dogs.

Animals—95 dogs with ruptured CCL, 8 dogs with experimentally ruptured CCL, and 24 healthy dogs.

Procedure—Synovial fluid was assayed for chondroitin sulfate neo-epitopes 3B3(–) and 7D4 and glycosaminoglycan (GAG) concentration. Results were correlated with demographic data, duration of lameness, radiographic osteoarthritis score, and intra-articular lesions.

Results—The 7D4 concentrations and 7D4:GAG in synovial fluid from joints with naturally acquired CCL rupture and experimental CCL transection were similar and significantly greater than values for healthy control joints. The 3B3(–) concentrations in the CCL-deficient groups were not significantly different, although only values in the naturally acquired CCL rupture group were significantly greater than those in the healthy control group. Within the naturally acquired CCL rupture group there was a significant correlation between 3B3(–) and 7D4 concentrations. However, there were no significant correlations between biomarker concentrations and continuous demographic or diseaserelated variables or differences in biomarker concentrations with different categories of disease.

Conclusion and Clinical Relevance—Synovial fluid biomarker concentrations were significantly increased in joints with secondary osteoarthritis associated with naturally acquired or experimental CCL rupture; however, lack of apparently simple relationships with demographic variables or stage or severity of disease limits their clinical usefulness. (Am J Vet Res 2002;63:775–781)

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in American Journal of Veterinary Research