Objective. To investigate the appearance of hypertrophic chondrocytes in osteoarthritic (OAj cartilage, using type X collagen as a specific marker.Methods. The biosynthesis of type X collagen was examined by metabolic labeling of freshly isolated articular chondrocytes with 3H-proline, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the synthesized collagens. Extracellular deposition of types X and I1 collagen was analyzed immunohistochemically . Chondrocytes of normal adult articular cartilage are phenotypically similar to fetal chondrocytes of the resting zone, in that they synthesize the same pattern of collagens: types 11, IX, XI, and VI ( 1 4 ) . There are conflicting reports concerning the modulation of the chondrocyte phenotype and associated alterations of collagen synthesis during osteoarthritic (OA) degeneration of articular cartilage. In early stages of human and experimentally induced OA, articular chondrocytes respond to the degenerative events by increasing the synthesis of proteoglycan and type I1 collagen several times higher than normal (5,6); this suggests stability of the chondrocyte phenotype. Other investigators have observed that chondrocytes in the upper zone of OA cartilage stain pericellularly with antibodies to types 1 and I11 collagen (7). Biochemical analyses of articular cartilage, however, have clearly shown that more than 95% of the collagen in both normal and OA cartilage is type I1 collagen, while significant amounts of type I collagen are found only in fibrocartilage (3,8). ResultsThe frequent occurrence of clusters of proliferating, hypertrophic chondrocytes in OA cartilage (9) prompted us to search for type X collagen during various stages of osteoarthritic degeneration of cartilage. Type X collagen is a short, non-fibril-forming collagen which has thus far been found only in hyper-

The objective of this study was to investigate the expression and extracellular distribution of fibrillar collagen types I, II, and III in early stage osteoarthritic cartilage in order to elucidate matrix gene expression and cell differentiation in early phases of the disease. Arthroscopically, derived specimens of early stage osteoarthritic articular cartilage were analyzed by histochemistry, immunohistochemistry and by in situ hybridization and compared with normal articular cartilage samples. In normal articular cartilage no significant mRNA expression of any of the investigated collagen types was found. In early stage osteoarthritic specimens, a strongly enhanced mRNA expression of the major cartilage matrix component type II collagen was detected. Additionally, a focal onset of type III, but not type I collagen expression was observed. Thus, besides activation of matrix synthesis, the modulation of the chondrocytic phenotype is likely to play a distinct role in the cellular response in the early phases of the degenerative process in osteoarthritis.

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