DIFFERENTIAL EXPRESSION OF COLLAGENASE BY HUMAN FIBROBLASTS AND BONE-MARROW STROMAL CELLS

The bone marrow stroma, represented in long-term marrow culture by cel ls of the adherent layer, is composed of a heterogenous mixture of mac rophages and mesenchymal cells, including fibroblasts, endothelial cel ls and adipocytes, in association with a proteoglycan matrix. This mat rix, which is synthesized by the stroma, is capable of binding hematop oietic growth factors, and likely plays a major role in hematopoietic regulation. Clonally-derived non-transformed bone marrow stromal cells , propagated in the presence of basic fibroblast growth factor, were s tudied for expression of collagenase, an enzyme whose substrate, colla gen, is a major component of the extracellular matrix. Expression of s teady-state collagenase mRNA was undetectable in both unstimulated der mal fibroblasts and non-transformed marrow stromal cells. However, sti mulation with interleukin 1 alpha (10 U/ml) for 24 h resulted in marke d accumulation of collagenase mRNA in dermal fibroblast cells, yet fai led to elicit a similar response in bone marrow stromal cells. Both ma rrow stromal cells and dermal fibroblasts constitutively expressed tra nscripts of collagen I, and rhIL-1 alpha upregulated transcripts of in terleukin 6 in both these cells as well. Although similar in morpholog y, these data indicate that bone marrow stromal cells differ from fibr oblasts in their response to IL-l. In the marrow microenvironment, whe re IL-l may be secreted by a variety of cell types, such suppression o f collagenase expression may serve to prevent unwanted mobilization of collagen from the glycoprotein matrix by marrow stromal cells.