CATHEPSIN-B IN OSTEOARTHRITIS - ZONAL VARIATION OF ENZYME-ACTIVITY INHUMAN FEMORAL-HEAD CARTILAGE

Objectives-To determine the quantitative topographical distribution of cathepsin B in human femoral head cartilage by measuring the zonal va riation of enzyme activity in specimens taken from various anatomical regions of normal and osteoarthritic (OA) tissues, and to correlate th is parameter with the severity of the OA lesions. Methods-OA articular cartilage was obtained at surgery for total hip replacement and contr ol cartilage obtained at postmortem. Cylinders of full thickness carti lage with underlying bone were retrieved with a biopsy trephine. Secti ons of cartilage were produced by cryocutting the tissue as slices par allel to the articular surface and assayed for cathepsin B with a spec ific, highly sensitive fluorogenic substrate. The severity of the OA l esions was graded according to the histopathological-histochemical met hod of Mankin. Results-Zonal cathepsin B activity of normal cartilage was uniform and low in all regions of the femoral head. In apparently intact OA cartilage and in severely degraded tissue the zonal distribu tion and the amounts of enzyme were similar to control values. At site s with active disease, cathepsin B activity was much greater than in c ontrols and its irregular zonal distribution correlated with tissue de generation, hypercellularity, or cloning of chondrocytes as determined histochemically. Particularly high enzyme levels were observed at sit es with regenerating cartilage, where some zonal peaks attained 20-fol d activity with respect to controls. Conclusion-Cathepsin B may play a role in sustaining the chronicity of OA, not as an initiator, but rat her as a perpetuator of the disease and as an antagonist of regenerati on.