Bacterial lipopolysaccharides induce in vitro degradation of cartilage matrix through chondrocyte activation

Abstract

The present studies demonstrate that bacterial lipopolysaccharides (LPS) induce cartilage matrix degradation in live explants in organ culture. Quintuplicate bovine nasal fibrocartilage explants cultured for 8 d with three different purified LPS preparations derived from Escherichia coli and Salmonella typhosa at concentrations ranging from 1.0 to 25.0 μg/ml resulted in matrix proteoglycan depletion of 33.3 ± 5.8 to 92.5 ± 2.0% (medium control depletion 17.7 ± 0.7 to 32.4 ± 1.4%). Matric degradation depended on the presence of live chondrocytes because frozen-thawed explants incubated with LPS failed to show any proteoglycan release. Moreover, the addition of Polymyxin B (25 μg/ml) to live explants incubated with LPS abolished matrix release, whereas Polymyxin B had no effect on the matrix-degrading activity provided by blood mononuclear cell factors. A highly purified Lipid A preparation induced matrix degradation at a concentration of 0.01 μg/ml. Cartilage matrix collagen and proteoglycan depletion also occurred with porcine articular cartilage explants (collagen release: 18.3 ± 3.5%, medium control: 2.1 ± 0.5%; proteoglycan release: 79.0 ± 5.9%, median control: 28.8 ± 4.8%). Histochemical analysis of the cultured explants confirmed the results described above. Gel chromatography of the proteoglycans released in culture indicated that LPS induced significant degradation of the high molecular weight chondroitin sulfate-containing aggregates. These findings suggest that bacterial products may induce cartilage damage by direct stimulation of chondrocytes. This pathogenic mechanism may play a role in joint damage in septic arthritis and in arthropathies resulting from the presence of bacterial products derived from the gastrointestinal tract.