SUSCEPTIBILITY OF STROMELYSIN 1-DEFICIENT MICE TO COLLAGEN-INDUCED ARTHRITIS AND CARTILAGE DESTRUCTION

Objective. It has long been proposed that stromelysin is one of the ma jor degradative matrix metalloproteinases responsible for the loss of cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). This h ypothesis was tested by examining the arthritic paws of stromelysin 1 (SLN1)-deficient mice for loss of cartilage and for generation oft neo epitopes that would be indicative of aggrecan cleavage. Methods. The S LN1 gene was inactivated in murine embryonic stem cells, and knockout mice deficient in SLN1 activity were bred onto the B10.RIII background . The incidence and severity of collagen-induced arthritis (CIA) were compared in wild-type and knockout mice. Paws from mice with CIA were examined for loss of cartilage and for proteoglycan staining, as well as for-the generation of the neoepitope FVDIPEN341. Results. SLN1-defi cient mice developed CIA, as did the wild-type N2 mice. Histologic ana lyses demonstrated no significant differences among the B10.RIII, wild -type, and knockout mice in loss of articular cartilage and proteoglyc an staining, No decrease in the FVDIPEN341 epitope was observed in the SLN1-deficient mice. Conclusion. Disruption of the SLN1 gene neither prevents nor reduces the cartilage destruction associated with CIA, Mo reover, SLN1 depletion does not prevent the cleavage of the aggrecan A sn(341)-Phe(342) bond.