Role of the captured retroviral envelope gene in the fusion of osteoclast and giant cell precursors and in bone resorption, analyzed and in knockout mice.

and are envelope genes of retroviral origin that have been captured in evolution for a role in placentation. They trigger cell-cell fusion and were shown to be essential for the formation of the syncytiotrophoblast layer during mouse placenta formation. and expression has been described in other tissues and their highly fusogenic properties suggested that they might be involved in the fusion of other cell types. Here, taking advantage of mice knocked out for , SynB mice, we investigated the potential role of in the fusion of cells from the monocyte/macrophage lineage into multinucleated osteoclasts (OCs) -in bone- or multinucleated giant cells -in soft tissues. In experiments, a significant reduction in fusion index and in the number of multinucleated OCs and giant cells was observed as soon as Day3 in SynB as compared to wild-type cell cultures. Interestingly, the number of nuclei per multinucleated OC or giant cell remained unchanged. These results, together with the demonstration that expression is maximal in the first 2 days of OC differentiation, argue for playing a role in the fusion of OC and giant cell mononucleated precursors, at initial stages. Finally, , the observed reduction in multinucleated OC number had no impact on the expression of OC differentiation markers, and a dentin resorption assay did not evidence any difference in the osteoclastic resorption activity, suggesting that is not required for OC activity. , was found to be expressed in the periosteum of embryos at embryonic day 16.5, where TRAP-positive cells were observed. Yet, in adults, no significant reduction in OC number or alteration in bone phenotype was observed in SynB mice. In addition, SynB mice did not show any change in the number of foreign body giant cells (FBGCs) that formed in response to implantation of foreign material, as compared to wild-type mice. Altogether the results suggest that in addition to its essential role in placenta formation, plays a role in OCs and macrophage fusion; yet it is not essential for OC and FBGC formation, or maintenance of bone homeostasis, at least under the conditions tested.