Multinucleation enhances macrophage-mediated bone resorption

M. D. Fallon, S. L. Teitelbaum, A. J. Kahn

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 < 0.001). Similarly, 'clast-like polykaryons resorb both large (24 to 43 μm diameter) and small (≤ 24 μm) particles more efficiently than age- and culture condition-matched mononuclear cells (treated to control ratios, 1.3 to 4.2:1, p < 0.001). This difference in degradative activity remains highly significant whether resorption (45Ca release) is expressed per microgram of DNA, per 100 μg 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.

Original languageEnglish
Pages (from-to)159-164
Number of pages6
JournalLaboratory Investigation
Volume49
Issue number2
StatePublished - Jan 1 1983

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