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 α1β1 and α2β1 in this process, we used three different osteogenic cell lines with distinct patterns of putative collagen receptors: HOS cells, which express only α1β1 integrin, MG-63 cells, which express only α2β1 integrin, and KHOS-240 cells, which express both. Inside collagen gels, α1(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 α2 integrin cDNA produced cell clones overexpressing α2β1 integrin. Transfection of MG-63 cells with α2 integrin cDNA in an antisense orientation reduced the expression level of α2 integrin. These cell clones showed induction and reduction of mRNA levels for MMP-1, respectively. HOS cells normally lacking α2β1 integrin were forced to express it, and this prevented the down-regulation in the levels of α1(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 α2β1 integrin. The down-regulation of collagen α1(I) is mediated by another receptor. Integrin α2β1 may compete with it and thus be a positive regulator of collagen synthesis.
This work was supported in part by grants from the Academy of Finland, the Sigrid Jusélius Foundation, the Paulo Foundation, the Turku University Foundation, the Finnish Cancer Association, and the SWF Cancer Research Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
