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

Abstract

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 ug/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%, medium 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 sulfatecontaining 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

Toll‐like receptors and chondrocytes: The lipopolysaccharide‐induced decrease in cartilage matrix synthesis is dependent on the presence of toll‐like receptor 4 and antagonized by bone morphogenetic protein 7

“…It is generally accepted that LPS from gram-negative bacteria stimulates an inflammation response (28,29). Moreover, LPS was previously shown to induce matrix breakdown in articular cartilage explants (17)(18)(19) and is widely used as a catabolic molecule in cell culture. Likewise, the presence of IL-1␤ leads to reductions in biosynthetic activity.…”

“…Given the previously described catabolic effects of lipopolysaccharide (LPS) on cartilage matrix (17)(18)(19), we particularly focused on the LPS-induced activation of TLR-4, the receptor for LPS, in human and murine articular chondrocytes. Our results consistently showed the expression of TLR-4 in human articular chondrocytes on both the messenger RNA (mRNA) and protein level.…”

Inflammatory bowel disease and spondylarthropathy

“…If similar antigens are present in the bowel, then increased bowel permeability might predispose to the development of an autoimmune response. Bacterial lipopolysaccharides damage cartilage by activating chondrocytes, which could reveal "neo"-antigens and thus provide an indirect pathway for bacterial products to initiate autoimmunity (82). The presence of proteoglycan-specific T lymphocytes in AS patients has been demonstrated (83), and arthritogenic T cell lines have been found to cross-react between purified protein derivative of Mycobacterium, for example, and cartilage proteoglycan (84).…”

Modulation of cartilage destruction by select nonsteroidal antiinflammatory drugs

“…This nonviable substrate was used to measure proteoglycan-degrading enzyme activity in SCM, whereas viable cartilage provided an index of catabolism-inducing activity as well. Lipopolysaccharide (25 pg/ml) was used in assays as a positive control because of its ability to induce chondrocyte proteinase release (29). Cultures were maintained at 37"C, in 5% COz and 95% air for 6 days.…”