Influence of the severity and duration of murine antigen-induced arthritis on cartilage proteoglycan synthesis and chondrocyte death.

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.