IDENTIFICATION OF THE MEMBRANE-TYPE MATRIX METALLOPROTEINASE MT1-MMP IN OSTEOCLASTS

The osteoclasts are the cells responsible for bone resorption. Matrix metalloproteinases (MMPs) appear crucial for this process. To identify possible MMP expression in osteoclasts, we amplified osteoclast cDNA fragments having homology with MMP genes, and used them as a probe to screen a rabbit osteoclast cDNA library. We obtained a cDNA of 1,972 b p encoding a polypeptide of 582 amino acids that showed more than 92% identity to human, mouse, and rat membrane-type 1 MMP (MT1-MMP), a cel l surface proteinase believed to trigger cancer cell invasion. By nort hern blotting, MT1-MMP was found to be highly expressed in purified os teoclasts when compared with alveolar macrophages and bone stromal cel ls, as well as with various tissues. In situ hybridization on bone sec tions showed that MT1-MMP is expressed also in osteoclasts in vivo. An tibodies recognizing MT1-MMP reacted with specific plasma membrane are as corresponding to lamellipodia and podosomes involved, respectively, in migratory and attachment activities of the osteoclasts. These obse rvations highlight how cells might bring MT1-MMP into contact with foc al points of the extracellular matrix, and are compatible with a role of MT1-MMP in migratory and attachment activities of the osteoclast.