MULTINUCLEATION ENHANCES MACROPHAGE-MEDIATED BONE-RESORPTION

Abstract

Degradation of mineralized connective tissues in vivo is a function of multinucleated giant cells (''clasts) derived from and belonging to the mononuclear phagocyte family. To determine if attainment of the multinucleated state is causally or only coincidentally related to ''clast degradative activity, ''clast-like polykaryons were produced by exposing elicited rat macrophages to human serum (10% for 7-14 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 vs. approximately 25%; P < 0.001). Similarly, ''clast-like polykaryons resorb large (24-43-.mu.m diameter) and small (.ltoreq. 24-.mu.m) particles more efficiently than age- and culture condition-matched mononuclear cells (treated to control ratios, 1.3-4.2:1, P < 0.001). This difference in degradative activity remains highly significant whether resorption (45Ca release) is expressed per microgram DNA, per 100 .mu.g of protein or per total cell surface area. Multinucleation produces qualitative changes in the resorptive capacity of macrophagic cells. Apparently, formation of polykaryons is a physiologically important event in ''clast development.