Differential expression of collagenase by human fibroblasts and bone marrow stromal cells.
The bone marrow stroma, represented in long-term marrow culture by cells of the adherent layer, is composed of a heterogenous mixture of macrophages and mesenchymal cells, including fibroblasts, endothelial cells and adipocytes, in association with a proteoglycan matrix. This matrix, which is synthesized by the stroma, is capable of binding hematopoietic 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 studied for expression of collagenase, an enzyme whose substrate, collagen, is a major component of the extracellular matrix. Expression of steady-state collagenase mRNA was undetectable in both unstimulated dermal fibroblasts and non-transformed marrow stromal cells. However, stimulation with interleukin 1 alpha (10 U/ml) for 24 h resulted in marked accumulation of collagenase mRNA in dermal fibroblast cells, yet failed to elicit a similar response in bone marrow stromal cells. Both marrow stromal cells and dermal fibroblasts constitutively expressed transcripts of collagen I, and rhIL-1 alpha upregulated transcripts of interleukin 6 in both these cells as well. Although similar in morphology, these data indicate that bone marrow stromal cells differ from fibroblasts in their response to IL-1. In the marrow microenvironment, where IL-1 may be secreted by a variety of cell types, such suppression of collagenase expression may serve to prevent unwanted mobilization of collagen from the glycoprotein matrix by marrow stromal cells.
Takahashi
G W
GW
Medical Service, Veterans Administration Medical Center, Seattle, Washington.
Moran
D
D
Andrews
D F
DF
Singer
J W
JW
D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D003094:Collagen; D017364:Collagenases