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Decorin is a small extracellular chondroitin/dermatan sulfate proteoglycan that has previously been shown to be involved in the angiogenesis-like behavior of endothelial cells (ECs) in vitro. There is also evidence that decorin plays a role in angiogenesis in vivo. In this study we sought to further explore the involvement of decorin in angiogenesis in vivo, especially in that associated with inflammation. We found by CD31 immunostaining of ECs that in giant cell arteritis there are capillary blood vessels not only in the adventitia as in uninvolved temporal artery wall, but also in the media and the external zone of the thickened intima. Localization of decorin by antiserum LF-30 in adjacent sections showed that in normal temporal artery wall decorin resides mainly in the media and the adventitia, whereas in inflamed temporal artery wall decorin is distributed throughout the vessel wall including the intima. Furthermore, the most intense reaction for decorin was evident in ECs of capillary neovessels within the media and the thickened intima of inflamed temporal artery wall. Decorin was also found in capillary ECs in certain pathological and physiological conditions in which the pivotal role of angiogenesis is more generally accepted. Pyogenic granulomas, granulation tissue of healing dermal wounds, and ovaries at different phases of follicle and corpus luteum formation all contained widely distributed CD31-positive capillaries. Decorin, on the other hand, was found in capillary ECs in pyogenic granulomas and granulation tissue, but not in those in the ovaries. The assessment of the degree of inflammation in the specimens with the presence of CD68-positive macrophages showed that the pyogenic granuloma, granulation tissue, and giant cell arteritis specimens were rich in macrophages around the decorin-positive capillaries. In contrast, the ovarian specimens were populated with fewer macrophages and even they were not located in close vicinity of capillaries negative for decorin. Our results confirm that decorin is involved in angiogenesis in vivo and, particularly, in conditions in which the inflammatory component is dominant.

Objectives: To study the expression of cysteine proteinases, particularly cathepsin K, and their extracellular inhibitor cystatin C in articular cartilage of transgenic Del1 mice which harbour a short deletion mutation in a type II collagen transgene and are predisposed to early onset osteoarthritis. Methods: Northern analysis was used to measure mRNA levels of cathepsins B, H, K, L, and S, and cystatin C in total RNA extracted from knee joints of Del1 mice, using their non-transgenic litter mates as controls. Immunohistochemistry and morphometry was used to study the distribution of cathepsin K and cystatin C in the knee joints. Results: Up regulation of cathepsin K mRNA expression was seen in the knee joints of transgenic Del1 mice at the onset of cartilage degeneration. Cathepsin K was found near sites of matrix destruction in articular chondrocytes, particularly in clusters of proliferating cells, and in calcified cartilaginous matrix. In intact articular cartilage of control animals, cathepsin K was only seen in a small number of chondrocytes. Upon aging, control animals also developed osteoarthritis, which was accompanied by increased cathepsin K expression. Cystatin C was mostly localised in and around chondrocytes located in calcified cartilage, with no obvious association with the onset of cartilage degeneration. Conclusion: The temporospatial distribution of cathepsin K in osteoarthritic cartilage suggests a role for this enzyme in the pathogenesis of osteoarthritis. Because cathepsin K can digest cartilage matrix components it may contribute to the development of osteoarthritic lesions. These data may provide new clues for the development of treatments aimed at preventing cartilage degeneration.

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Objective To determine the capacity of chondrocytes in aging and degenerating articular cartilage to produce major components of the extracellular matrix and maintain the normal structure of articular cartilage in a transgenic mouse model of osteoarthritis. Methods Transcription factor Sox9 was used as an indicator of the activation and maintenance of the articular chondrocyte phenotype. Knee joints of Del1 mice carrying 6 copies of the proα1(II) collagen transgene with a short deletion mutation were analyzed at the age of 10 days and at 2, 3, 4, 6, 9, and 15 months by Northern hybridization, RNase protection assay, quantitative reverse transcription–polymerase chain reaction, and immunohistochemistry. Nontransgenic littermates were used as controls. Results We demonstrated the presence of Sox9 in articular chondrocytes during development, growth, and aging, with the highest messenger RNA levels during the period of rapid growth. With the appearance of degenerative lesions in articular cartilage, 2 repair processes were observed. Local proliferation and activation of chondrocytes rich in Sox9, surrounded by type IIA procollagen and proteoglycans, was seen in articular cartilage. In contrast, metabolically inactive chondrocytes were observed at the margins of the defects. They were devoid of Sox9 and were surrounded by a proteoglycan‐poor matrix. Sometimes, the lesions were filled with repair tissue that contained type III collagen but little proteoglycan or type II collagen. Conclusion The results indicate that chondrocytes in mature articular cartilage are capable of inducing the production of Sox9 and type IIA procollagen, which is typical of early chondrogenesis. Degenerative defects in the knee joints of transgenic Del1 mice are associated with local activation of chondrocytes, which probably contributes to the repair process. In other areas, the repair process produces a noncartilaginous matrix, which is insufficient to maintain the integrity of articular cartilage and which allows degeneration to proceed.