Recent studies have shown that joint
inflammation can suppress chondrocyte
proteoglycan synthesis and can even kill chondrocytes. In the present study, we investigated the influence of the severity and chronicity of murine
antigen-induced
arthritis on the degree of these toxic effects on chondrocytes. Joint
inflammation, quantitated by measurements of
99m technetium pertechnetate uptake, was significantly correlated with the inhibition of
proteoglycan synthesis, measured by 35S-sulfate incorporation. Histologic grading of the extent of chondrocyte death on day 28 after
arthritis induction correlated best with the degree of
inflammation present on day 14. High scores for chondrocyte death were found only in mice with persistent, severe
arthritis. Our data indicate that the severity of joint
inflammation is a major determinant of the degree of chondrocyte
proteoglycan synthesis inhibition, whereas both the severity and chronicity of the
inflammation determine chondrocyte killing and, therefore, irreversible joint destruction.