The action of cathepsin D in human articular cartilage on proteoglycans

have been implicated as important agents in the physio-logical degradation of various cartilages. In the present study, the nature of cathepsin present in human articu-lar cartilage was investigated by microtechniques and a possible role for cathepsins in the cartilage degradation observed in osteoarthritis was sought. The results of this study indicated that the hemoglobin and proteo-glycan-digesting activity in the human cartilage ob-served is predominantly that of a cathepsin D-type en-zyme. This cathepsin D-type enzyme activity was present in two to three times greater amounts in yellowish or ulcerated articular cartilage from patients with primary osteoarthritis than in control "normal " human cartilages. The human cathepsin D-type enzyme, as well as a highly purified cathepsin D from bovine uterus degraded pro-teoglycan subunit (PGS) maximally at pH 5. Both en-zyme preparations were inactive on hemoglobin at pH 6-8, but degraded PGS considerably at neutral pH. The activity of the human cathepsin extract was not affected by reagents which inhibit or activate cathepsins A and B. Neutral proteases which are active on hemoglobin or are inhibited by diisopropylfluorophosphate (DFP) were not detected in these preparations, but contamination by another type of neutral protease cannot be excluded. Chloroquine inhibited the degradation of PGS at neu-tral pH by the human cartilage enzyme extract