Cathepsin B in osteoarthritis: cytochemical and histochemical analysis of human femoral head cartilage.
OBJECTIVE
To localise the cysteine endopeptidase cathepsin B in chondrocytes and cartilage from normal and osteoarthritic (OA) human femoral heads in order to provide qualitative information on its cellular expression and distribution at possible sites of action.


METHODS
OA articular cartilage was obtained at surgery for total hip replacement; control cartilage was obtained at postmortem. Chondrocytes were isolated by sequential enzymatic digestion and cathepsin B analysed by immunocytochemistry and activity staining with a fluorogenic substrate. Lysosomes were visualised by fluorescence microscopy after staining of living cells with acridine orange. Using a histochemical reaction, enzyme activity was measured in cryosections of full thickness cartilage.


RESULTS
Chondrocytes from normal cartilage contained very few lysosomes and only a minor cell population was cathepsin B positive. A high proportion of chondrocytes from active OA cartilage contained a large number of lysosomes and an excess of cathepsin B in intracellular organelles; the enzyme was stored in an active form. In this respect, OA chondrocytes closely resembled normal cells that had been phenotypically modulated by serial subcultures. No cathepsin B activity could be detected by histochemistry in either chondrocytes or matrix of normal cartilage. While apparently intact and severely degraded OA cartilage was also cathepsin B negative, tissue at sites of active destruction and, particularly, at repair sites was highly positive.


CONCLUSIONS
The presence and the particular distribution of active cathepsin B in OA cartilage at 'more involved' sites suggest a pathological role for this enzyme in sustaining and perpetuating cartilage degradation. While other stimuli may also be responsible for cathepsin B expression in OA chondrocytes, the similarity with artificially modulated cells indicates fibroblastic metaplasia as a plausible mechanism.
Baici
A
A
Department of Rheumatology, University Hospital, Zurich, Switzerland.
Lang
A
A
Hörler
D
D
Kissling
R
R
Merlin
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000201:enzymology*; D002401:Cathepsin B / Q000032:analysis*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D005270:Femur Head / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015388:Organelles / Q000201:enzymology; D010003:Osteoarthritis / Q000201:enzymology*
D002401:Cathepsin B