A. Baici et al., CATHEPSIN-B IN OSTEOARTHRITIS - CYTOCHEMICAL AND HISTOCHEMICAL ANALYSIS OF HUMAN FEMORAL-HEAD CARTILAGE, Annals of the Rheumatic Diseases, 54(4), 1995, pp. 289-297
Objective-To localise the cysteine endopeptidase cathepsin B in chondr
ocytes and cartilage from normal and osteoarthritic (OA) human femoral
heads in order to provide qualitative information on its cellular exp
ression and distribution at possible sites of action. Methods-OA artic
ular cartilage was obtained at surgery for total hip replacement; cont
rol cartilage was obtained at postmortem. Chondrocytes were isolated b
y sequential enzymatic digestion and cathepsin B analysed by immunocyt
ochemistry and activity staining with a fluorogenic substrate. Lysosom
es were visualised by fluorescence microscopy after staining of living
cells with acridine orange. Using a histochemical reaction, enzyme ac
tivity was measured in cryosections of full thickness cartilage. Resul
ts-Chondrocytes from normal cartilage contained very few lysosomes and
only a minor cell population was cathepsin B positive. A high proport
ion 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 chondroc
ytes closely resembled normal cells that had been phenotypically modul
ated 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, parti
cularly, at repair sites was highly positive. Conclusion-The presence
and the particular distribution of active cathepsin B in OA cartilage
at 'more involved' sites suggest a pathological role for this enzyme i
n sustaining and perpetuating cartilage degradation. While other stimu
li may also be responsible for cathepsin B expression in OA chondrocyt
es, the similarity with artificially modulated cells indicates fibrobl
astic metaplasia as a plausible mechanism.