Cell-surface phosphatidylserine regulates osteoclast precursor fusion.

Abstract

Bone-resorbing multinucleated osteoclasts that play central role in the maintenance and repair of our bones are formed from bone marrow myeloid progenitor cells by a complex differentiation process that culminates in fusion of mononuclear osteoclast precursors. In this study, we uncoupled the cell fusion step from both pre-fusion stages of osteoclastogenic differentiation and the post-fusion expansion of the nascent fusion connections. We accumulated ready-to-fuse cells in the presence of a fusion inhibitor lysophosphatidylcholine and then removed the inhibitor to study synchronized cell fusion. We found that osteoclast fusion required the dendrocyte-expressed seven transmembrane protein (DC-STAMP)-dependent non-apoptotic exposure of phosphatidylserine at the surface of fusion-committed cells. Fusion also depended on extracellular annexins, phosphatidylserine-binding proteins, which, along with annexin-binding protein S100A4, regulated fusogenic activity of syncytin 1. Thus, in contrast to fusion processes mediated by a single protein, such as epithelial cell fusion in C. elegans, the cell fusion step in osteoclastogenesis is controlled by a phosphatidylserine-regulated activity of several proteins.

DOI: 10.1074/jbc.M117.809681

Cite this paper

@article{Verma2017CellsurfacePR, title={Cell-surface phosphatidylserine regulates osteoclast precursor fusion.}, author={Santosh kumar Verma and Evgenia Leikina and Kamran C Melikov and Claudia M. Gebert and Vardit Kram and Marian Francis Young and Berna Uygur and Leonid V. Chernomordik}, journal={The Journal of biological chemistry}, year={2017} }