Cathepsin B in osteoarthritis: cytochemical and histochemical analysis of human femoral head cartilage

• Published in: Annals of the rheumatic diseases Vol. 54; no. 4; pp. 289 - 297
• Main Authors: Baici, A, Lang, A, Hörler, D, Kissling, R, Merlin, C
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.04.1995; BMJ; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cartilage, Articular - enzymology; Cathepsin B - analysis; Cells, Cultured; Diseases of the osteoarticular system; Extracellular Matrix - enzymology; Female; Femur Head - enzymology; Humans; Immunoenzyme Techniques; Lysosomes - enzymology; Male; Medical sciences; Microscopy, Fluorescence; Middle Aged; Organelles - enzymology; Osteoarthritis; Osteoarthritis - enzymology; Human; Chondrocyte; Femoral head; Enzyme; Cysteine endopeptidases; Diseases of the osteoarticular system; Exploration; Cytochemistry; Hip; Pathology; Cartilage; Enzymatic activity; Distribution; Arthropathy; Cathepsin B; Hydrolases; Extracellular matrix; Degenerative disease; Proteinases; Osteoarthritis; Histochemistry
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.54.4.289

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. 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 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.