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Fusion of preosteoclasts to generate multinucleated osteoclasts is defective in the absence of DC-STAMP (right).

Bone-resorbing osteoclasts can't pull together in the absence of dendritic cell–specific transmembrane protein (DC-STAMP), according to new data from Yagi and colleagues (page 345). Without this receptor, osteoclast precursor cells cannot fuse with one another. The failure to fuse cripples the bone resorbing function of the cells, causing osteopetrosis (increased bone mass).

DC-STAMP is a seven-transmembrane–spanning receptor that was originally isolated from dendritic cells (DCs). The ligand for DC-STAMP and its function on DCs are unknown, but this receptor was recently found on osteoclasts and shown to be required for these cells to develop from their macrophage precursors.

Yagi and colleagues now refine these data by showing that multinucleated osteoclasts were completely absent in the bones of mice lacking DC-STAMP, although osteoclast development was intact. The DC-STAMP–deficient mice suffered from mild osteopetrosis, as mononucleated osteoclasts can still resorb bone. Whether DC-STAMP triggers fusion directly or triggers the expression of other fusion-inducing receptors remains to be determined.

The absence of DC-STAMP also inhibited the formation of foreign body giant cells—products of macrophage fusion that dispose of foreign bodies in tissues. Although the mechanism is not yet known, DC-STAMP may function as a fusion coreceptor in a fashion analogous to the fusion of HIV with target cells, which depends on seven-transmembrane–spanning chemokine receptors (see commentary from Vignery, on page 337).

hvanepps{at}rockefeller.edu

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DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells

Mitsuru Yagi, Takeshi Miyamoto, Yumi Sawatani, Katsuya Iwamoto, Naobumi Hosogane, Nobuyuki Fujita, Kozo Morita, Ken Ninomiya, Toru Suzuki, Kana Miyamoto, Yuichi Oike, Motohiro Takeya, Yoshiaki Toyama, and Toshio Suda
J. Exp. Med. 2005 202: 345-351. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 816K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Epps, H. L. Search for Related Content PubMed Articles by Van Epps, H. L. Related Collections Related Articles Social Bookmarking                            What's this?