The relative importance of cysteine peptidases in osteoarthritis.
OBJECTIVE
To assess the activity of cysteine peptidases in cultured human articular chondrocytes as well as in osteoarthritic (OA) cartilage and subchondral bone, and to interpret their relative importance in cartilage destruction and remodeling of the subchondral region.


METHODS
Intracellular and secreted cysteine peptidase activity was measured in chondrocytes using fluorimetric assays, and enzymes were immunolocalized using monospecific antibodies. Enzyme histochemistry in normal and OA femoral heads was used to characterize enzymatic activity in full thickness samples containing cartilage and subchondral bone. The zonal distribution of cathepsin activity was measured in tissue slices of normal and OA femoral heads cut parallel to the joint surface, using fluorogenic substrates.


RESULTS
Cathepsins B and L were localized by immunohistochemistry with lysosome-like structures in dedifferentiated chondrocytes. Free cysteine peptidase activity (i.e., not requiring prior activation), secreted and intracellularly stored by chondrocytes, was due to cathepsin B, while cathepsin L contributed a minor fraction of the total activity, and was seen only after activation at acidic pH. Histochemistry and activity measurements confirmed cathepsin B as the major, active cysteine peptidase in OA cartilage, particularly at sites where matrix neosynthesis took place. However, free cathepsin L and/or cathepsin K activity was found subchondrally in association with cathepsin B in osteophytes, in zones undergoing bone remodeling, and at sites of inflammation.


CONCLUSIONS
Cathepsin B, not cathepsin L or cathepsin K, is a candidate for articular cartilage catabolism in OA. While cathepsin K is the major osteoclastic cysteine peptidase, cathepsin L and cathepsin B may also participate in the remodeling processes of bone as well as in bone erosion by inflammatory cells.
Lang
A
A
Center for Experimental Rheumatology, University of Zurich, Switzerland.
Hörler
D
D
Baici
A
A
D000328:Adult; D002358:Cartilage, Articular / Q000201:enzymology / Q000473:pathology; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005260:Female; D005270:Femur Head / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D015207:Osteoarthritis, Hip / Q000201:enzymology* / Q000473:pathology
D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L