THE MIGRATION OF PURIFIED OSTEOCLASTS THROUGH COLLAGEN IS INHIBITED BY MATRIX METALLOPROTEINASE INHIBITORS

The most obvious proteolytic event controlled by the osteoclast is bon e matrix removal in the resorption compartment, Here, however, we inve stigated whether matrix metalloproteinase (MMP) activity of the osteoc last might be involved in its migration to its future bone resorption site, We seeded either nonpurified or purified osteoclasts onto either uncoated or collagen-coated dentine slices and cultured them in the p resence or absence of specific MMP inhibitors, When nonpurified osteoc lasts were cultured on uncoated dentine, MMP inhibitors did not preven t pit formation, as previously reported, However, when collagen-coated dentine was used, pit formation was strongly inhibited by MMP inhibit ors, The same results were obtained when performing these experiments with purified osteoclasts, thus demonstrating the ability of osteoclas ts by themselves to migrate through collagen via an MMP-dependent path way, This demonstration was confirmed by using collagen-coated invasio n chambers, In addition, the invasions were not, or only slightly, inh ibited by inhibitors of serine proteinases, cysteine proteinases, and carbonic anhydrase, though the latter two are well established bone re sorption inhibitors that strongly inhibited pit formation, It is concl uded that osteoclasts can migrate through collagen in the absence of o ther cells and that this migration relies on MMP activity, whereas oth er enzymes typically required for bone removal in the resorption compa rtment are not essential for migration, Some of the osteoclast MMPs mi ght thus be relevant to the migratory/invasive activity of the osteocl ast, rather than to its bone resorptive activity itself.