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Regulation and Interactions of MT1-MMP and MMP-20 in Human Odontoblasts and Pulp Tissue in vitro

¹ Institute of Dentistry, PO Box 5281, 90014 University of Oulu, Oulu, Finland;
² Department of Cytokine Biology, Forsyth Institute, Boston, MA, USA;
³ Oulu University Hospital, Oulu, Finland;
⁴ Oral Pathology Unit and Biomedicum, University of Helsinki, Laboratory Diagnostics, Helsinki University Central Hospital (HUCH), Helsinki, Finland;
⁵ Harvard-Forsyth Department of Oral Biology & Department of Cytokine Biology, Forsyth Institute, Boston, MA, USA;
⁷ Department of Endodontics, Faculty of Dentistry, University of Toronto, ON, Canada;

*corresponding author, palosaar{at}csc.fi

MT1-MMP is a cell-membrane-bound metalloenzyme that activates other proMMPs such as proMMP-2 and -13. We studied MT1-MMP expression in mature human odontoblasts and pulp tissue, the regulation of MT1-MMP expression by growth factors TGF-ß1 and BMP-2, and the activation of odontoblast-derived MMP-20 by MT1-MMP. MT1-MMP mRNA is expressed by native and cultured mature human odontoblasts and pulp tissue. Western blot analysis of human odontoblasts and pulp tissue detects 65- and 51-kDa pro- and active forms of MT1-MMP, and smaller truncated MT1-MMP forms. BMP-2 down-regulates MT1-MMP expression in odontoblasts and pulp tissue, while TGF-ß1, alone or with BMP-2, decreases MT1-MMP mRNA levels only slightly. We also demonstrate that MT1-MMP is capable of converting proMMP-20 into a form corresponding to the active MMP-20. In conclusion, this study demonstrates the expression and differential regulation of MT1-MMP in human dentin-pulp complex cells, and the activation of MMP-20 by MT1-MMP.

KEY WORDS: MMP • TGF-ß • BMP-2 • odontoblasts • pulp tissue • activation

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