Cathepsin B and cysteine protease inhibitors in human osteoarthritis.
The aim of this study was to determine the involvement of cathepsin B and its inhibitors in the proteolytic degradation of human osteoarthritic (OA) tissue. The characteristics of the cathepsin B found in both normal and OA cartilage and synovium were similar to those of the lysosomal cathepsin B. Two inhibitors of cysteine proteases were found with a molecular weight of 67,000 and 16,000 Da. The cartilage cathepsin B level of OA specimens (54.8 +/- 7.3 units/micrograms of DNA) was greater than the controls (39.8 +/- 3.2 units/micrograms of DNA). Mild-moderate graded samples (78.1 +/- 12.0 units/micrograms of DNA) had significantly higher levels of enzyme activity than the severely graded ones (31.4 +/- 3.9 units/micrograms of DNA, p less than 0.001) and controls (p less than 0.01). Compared to controls (2.3 +/- 0.4 units/mg of tissue w.w.), cysteine protease inhibitory activity in OA cartilage was decreased in specimens with severe lesions (1.5 +/- 0.2 units/mg of tissue). This was particularly noted in patients who had not received steroid injections (1.2 +/- 0.3 units/mg of tissue, p less than 0.05). In OA synovia, the cathepsin B level was greater (40.7 +/- 7.4 units/mg of tissue w.w., p less than 0.02) than in the controls (13.6 +/- 3.7 units/mg of tissue). The cysteine protease inhibitory activity was similar in OA synovium (1.7 +/- 0.2 units/mg of tissue w.w.) and in controls (1.5 +/- 0.3 units/mg of tissue). This data demonstrated an imbalance between the levels of cathepsin B and cysteine protease inhibitors in OA tissue. A decrease of specific inhibitors could be an important contributing factor, particularly in more severe lesions.
Martel-Pelletier
J
J
Department of Medicine, Université de Montréal, Quebec, Canada.
Cloutier
J M
JM
Pelletier
J P
JP
D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000032:analysis / Q000378:metabolism / Q000503:physiopathology; D002401:Cathepsin B / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D013583:Synovial Membrane / Q000032:analysis / Q000378:metabolism / Q000503:physiopathology
D015853:Cysteine Proteinase Inhibitors; D002401:Cathepsin B