METALLOPROTEINASE PRODUCTION BY RABBIT ARTICULAR-CARTILAGE - COMPARISON OF THE EFFECTS OF INTERLEUKIN-1-ALPHA IN-VITRO AND IN-VIVO

To assess the effects of interleukin-1 on intact articular cartilage i n vitro, explants from young and adult rabbits were cultured with inte rleukin-1 and the distributions of the matrix metalloproteinases and t issue inhibitor of metalloproteinases (TIMP-1) were investigated by in direct immunofluorescence microscopy. One to 2-week-old cartilage chon drocytes synthesized collagenase in response to pure or crude interleu kin-1 (monocyte conditioned medium), with subarticular cells most resp onsive. Collagenase synthesis was not stimulated in adult articular ch ondrocytes when explants were treated with either pure or crude interl eukin-1. Stromelysin, gelatinase and TIMP-1 could not be demonstrated within any zone of the cartilage, indicating that their synthesis was not stimulated by either pure or crude interleukin-1. The addition of fibroblast growth factors, either alone or in combination with interle ukin-1, did not modify these responses. These results contrast markedl y with observations on cultured chondrocyte monolayers, where interleu kin-1 treatment induces near co-ordinate expression of metalloproteina ses. To assess the effects of interleukin-1 in vivo, it was injected i nto adult rabbit knee joint spaces and the articular cartilage subsequ ently analysed for evidence of altered metalloproteinase production by immunocytochemistry. No significant increase in metalloproteinase or TIMP-1 synthesis by chondrocytes was detected, although the cartilage matrix showed a marked loss of toluidine blue metachromasia. We conclu de that metalloproteinases are not involved in the rapid loss of prote oglycan from cartilage matrix in these situations.