INTERLEUKIN-6 AND ITS SOLUBLE RECEPTOR CAUSE A MARKED INDUCTION OF COLLAGENASE-3 EXPRESSION IN RAT OSTEOBLAST CULTURES

Interleukin-6 (IL-6), a cytokine produced by skeletal cells, increases bone resorption, but its effects on collagenase expression are unknow n. We tested the effects of IL-6 and its soluble receptor on collagena se 3 expression in osteoblast enriched cells from fetal rat calvariae (Ob cells). IL-6 caused a small increase in collagenase mRNA levels, b ut in the presence of IL-6-soluble receptor (IL-6sR), IL-6 caused a ma rked increase in collagenase transcripts after 2-24 h. In addition, IL -6sR increased collagenase mRNA when tested alone. IL-6 and IL-6sR inc reased immunoreactive collagenase levels. Cycloheximide and indomethac in did not prevent the effect of IL-6 and IL-6sR on collagenase mRNA l evels. IL-6 and IL-6sR did not alter the decay of collagenase mRNA in transcriptionally arrested Ob cells and increased the levels of collag enase heterogeneous nuclear RNA and the rate of collagenase gene trans cription in Ob cells. IL-6 and IL-6sR increased collagenase 3 mRNA in MC3T3 cells but only modestly in skin fibroblasts. IL-6 and IL-6sR enh anced the expression of tissue inhibitor of metalloproteinases 1. In c onclusion, IL-6, in the presence of IL-6sR, increases collagenase 3 sy nthesis in osteoblasts by transcriptional mechanisms. This effect may contribute to the action of IL-6 on bone matrix degradation and bone r esorption.