Histologic assessment of cathepsin D in osteoarthritic cartilage.
The lysosomal endopeptidase cathepsin D is the most abundant proteinase in chondrocytes. Its significance in the pathogenesis of cartilage matrix proteoglycan (PG) degradation in osteoarthritis (OA) is unclear. The extracellular localization of cathepsin D and its potential spatial relationship to areas of PG depletion has been studied in human femoral head OA cartilage. Enzyme was identified by indirect immunofluorescence using rabbit antisera developed against a highly purified cathepsin D preparation. PG distribution was assessed in parallel sections by safranin O staining. Specimens were selected to include regions of cartilage having minimal structural and cellular alterations, severe reduction in thickness, hypocellularity, multicellular chondrocyte clusters and varying degrees of PG loss. Cathepsin D was identified in chondrocytes. When overlying fibrous connective tissue pannus was present, extracellular enzyme was predominantly localized to the cartilage-pannus interface. Cathepsin D could not be demonstrated extracellularly in areas of cartilage that were partially or totally devoid of PG. Chondrocytes in damaged regions, particularly in the superficial and upper transitional zones showing diffuse hypercellularity and/or "brood" clusters, contained increased enzyme staining. Results fail to support a role for cathepsin D in extracellular matrix PG degradation. The potential significance of this enzyme in the pathogenesis of OA would appear relegated to intracellular catabolism. Its intracellular increase at pathologic sites is consistent with enhanced catabolic activity in such regions.
D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007120:Immunochemistry; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism
D011509:Proteoglycans; D002402:Cathepsin D