Integrin alpha 2 beta 1 is a positive regulator of collagenase (MMP-1) and collagen alpha 1(I) gene expression.
A classical model for studying the effects of extracellular matrix is to culture cells inside a three-dimensional collagen gel. When surrounded by fibrillar collagen, many cell types decrease the production of type I collagen, and the expression of interstitial collagenase (matrix metalloproteinase-1; MMP-1) is simultaneously induced. To study the role of the collagen-binding integrins alpha 1 beta 1 and alpha 2 beta 1 in this process, we used three different osteogenic cell lines with distinct patterns of putative collagen receptors: HOS cells, which express only alpha 1 beta 1 integrin, MG-63 cells, which express only alpha 2 beta 1 integrin, and KHOS-240 cells, which express both. Inside collagen gels, alpha 1 (I) collagen mRNA levels were decreased in HOS and KHOS-240 cells but not in MG-63 cells. In contrast, MMP-1 expression was induced in KHOS-240 and MG-63 cells but not in HOS cells. Transfection of MG-63 cells with alpha 2 integrin cDNA in an antisense orientation reduced the expression level of alpha 2 integrin. These cell clones showed induction and reduction of mRNA levels for MMP-1, respectively. HOS cells normally lacking alpha 2 beta 1 integrin were forced to express it, and this prevented the down-regulation in the levels of alpha 1 (I) collagen mRNA when cells were grown inside collagen gels. The data indicate that the level of MMP-1 expression is regulated by the collagen receptor alpha 2 beta 1 integrin. The down-regulation of collagen alpha 1 (I) is mediated by another receptor. Integrin alpha 2 beta 1 may compete with it and thus be a positive regulator of collagen synthesis.
Riikonen
T
T
MediCity Research Laboratory, University of Turku, Finland.
Westermarck
J
J
Koivisto
L
L
Broberg
A
A
Kähäri
V M
VM
Heino
J
J
D003094:Collagen / Q000235:genetics*; D017364:Collagenases / Q000235:genetics*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D020781:Matrix Metalloproteinase 1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured
D016023:Integrins; D012333:RNA, Messenger; D038981:Receptors, Collagen; D003094:Collagen; D017364:Collagenases; D020781:Matrix Metalloproteinase 1