Proinflammatory cytokines have profound effects on the metabolism of chondrocytes cultured in vitro. We recently suggested that chondrocytes that are producing proteoglycans at a fast rate may make the tissue in which they reside more susceptible to undergo proteoglycan (PG)-depletion following exposure to cytokines and related factors. Using chondrocytes maintained in alginate beads, we also have observed that the metabolically active cell-associated matrix (CM) is more susceptible to interleukin-1 (IL-1) - induced PG depletion than the more voluminous but less metabolically active further removed matrix (FRM). Articular cartilage exposed to lipopolysaccharides (LPS) molecules present on the cell wall of gram-negative bacteria, undergo rapid depletion of PGs, both in-vitro and in-vivo. LPS is one of the major factors playing a role in the pathogenesis of Septic arthritis and Lyme arthritis.

The study revealed that chondrocytes synthesizing PG at a faster rate are more susceptible to LPS- and IL-1-induced inhibition of PG synthesis than chondrocytes synthesizing these hydrophilic molecules at a slower rate. It showed that the CM surrounding chondrocytes synthesizing at a faster rate also is more susceptible to LPSinduced PG catabolism. The results showed that the CM compartment is much more sensitive to the effects of LPS on both PG synthesis and degradation than the more voluminous FRM compartment. Also, the study provided evidence in support of the broad applicability of the advantages the alginate bead system and its metabolicallyactive CM provides to those interested in monitoring the effects of growth factors (that promote anabolic processes) and proinflammatory cytokines (that inhibit matrix formation and promote matrix degradation). This held true for cells cultured in alginate beads under a variety or culture conditions. The study also led to the most interesting discovery that dexamethasone completely blocked the LPS-induced increased loss of ³⁵SPGs that accumulated in the CM, however, it did not block the LPS-induced inhibition of ³⁵S-PG synthesis.