Macrophage fusion: the making of osteoclasts and giant cells

Abstract

The fusion of cells is a fundamental biological event that is essential for a variety of developmental and homeostatic processes. Fusion is required for the formation of multinucleated osteoclasts and giant cells, although the mechanisms that govern these processes are poorly understood. A new study now reveals an unexpected role for the receptor, dendritic cell-specific transmembrane protein (DC-STAMP), in this process. The potential mechanism by which DC-STAMP governs fusion and the implications of this finding will be discussed.

Figure 1.

Potential mechanism of fusion of preosteoclasts and of macrophages. Osteoclast precursor cells respond to the osteoclast differentiation factor RANKL, which induces the expression of DC-STAMP. The DC-STAMP–expressing osteoclast becomes the master fusing cell, which can fuse with a DC-STAMP–negative follower cell. The ligand for DC-STAMP may be membrane bound or soluble; a soluble ligand might be released by either of the fusion partners. DC-STAMP ligation may trigger fusion of the two cells directly or may trigger the expression of as yet unknown membrane-bound molecules (‘X’) that mediate fusion. A similar scenario may occur during the formation of giant cells in which macrophages respond to interleukin-4 by inducing the expression of DC-STAMP, which then facilitates fusion.