Multinucleation enhances macrophage-mediated bone resorption

Abstract

The degradation of mineralized connective tissues in vivo is a function of multinucleated giant cells ('clasts) derived from and belonging to the mononuclear phagocyte family. However, it is not known whether the attainment of the multinucleated state is causally or only coincidentally related to 'clast degradative activity. To address this issue, 'clast-like polykaryons were produced by exposing elicited rat macrophages to human serum (10% for 7 to 14 days). Pure populations (90%) of multinucleated cells and their mononuclear macrophage counterparts were then assessed for their ability to bind and degrade 45Ca-labeled, devitalized bone particles in vitro. Macrophage polykaryons bind bone particles significantly more effectively than ordinary elicited mononuclear macrophages (approximately 40% attachment versus approximately 25%; p less than 0.001). Similarly, 'clast-like polykaryons resorb both large (24 to 43 microns diameter) and small (less than or equal to 24 microns) particles more efficiently than age- and culture condition-matched mononuclear cells (treated to control ratios, 1.3 to 4.2:1, p less than 0.001). This difference in degradative activity remains highly significant whether resorption (45Ca release) is expressed per microgram of DNA, per 100 micrograms of protein, or per total cell surface area. We conclude that multinucleation produces qualitative changes in the resorptive capacity of macrophagic cells. The data suggest that the formation of polykaryons is a physiologically important event in 'clast development.