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(Received for publication, September 13, 1996, and in revised form, February 24, 1997)
From the Departments of Research and Medicine, Saint Francis
Hospital and Medical Center, Hartford, Connecticut 06105 and The
University of Connecticut School of Medicine,
Farmington, Connecticut 06030
Interleukin-6 (IL-6), a cytokine produced by
skeletal cells, increases bone resorption, but its effects on
collagenase expression are unknown. We tested the effects of IL-6 and
its soluble receptor on collagenase 3 expression in osteoblast-enriched
cells from fetal rat calvariae (Ob cells). IL-6 caused a small increase
in collagenase mRNA levels, but in the presence of IL-6-soluble
receptor (IL-6sR), IL-6 caused a marked increase in collagenase
transcripts after 2-24 h. In addition, IL-6sR increased collagenase
mRNA when tested alone. IL-6 and IL-6sR increased immunoreactive
collagenase levels. Cycloheximide and indomethacin did not prevent the
effect of IL-6 and IL-6sR on collagenase mRNA levels. IL-6 and
IL-6sR did not alter the decay of collagenase mRNA in
transcriptionally arrested Ob cells and increased the levels of
collagenase heterogeneous nuclear RNA and the rate of collagenase gene
transcription 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 enhanced the expression of tissue inhibitor of
metalloproteinases 1. In conclusion, IL-6, in the presence of IL-6sR,
increases collagenase 3 synthesis in osteoblasts by transcriptional
mechanisms. This effect may contribute to the action of IL-6 on bone
matrix degradation and bone resorption.
Volume 272, Number 18,
Issue of May 2, 1997
pp. 12144-12150
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
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