Role of the captured retroviral envelope syncytin-B gene in the fusion of osteoclast and giant cell precursors and in bone resorption, analyzed ex vivo and in vivo in syncytin-B knockout mice

Amélie E Coudert; François Redelsperger; Yasmine Chabbi-Achengli; Cécile Vernochet; Caroline Marty; Xavier Decrouy; Thierry Heidmann; Marie-Christine de Vernejoul; Anne Dupressoir

doi:10.1016/j.bonr.2019.100214

Role of the captured retroviral envelope syncytin-B gene in the fusion of osteoclast and giant cell precursors and in bone resorption, analyzed ex vivo and in vivo in syncytin-B knockout mice

Bone Rep. 2019 Jul 10:11:100214. doi: 10.1016/j.bonr.2019.100214. eCollection 2019 Dec.

Authors

Amélie E Coudert^{1

2}, François Redelsperger³, Yasmine Chabbi-Achengli¹, Cécile Vernochet³, Caroline Marty¹, Xavier Decrouy⁴, Thierry Heidmann³, Marie-Christine de Vernejoul¹, Anne Dupressoir³

Affiliations

¹ BIOSCAR, Unité Mixte de Recherche 1132, Institut National de la Santé et de la Recherche Médicale, Hôpital Lariboisière, Paris 75010, France.
² Laboratoire de Physiopathologie Orale Moléculaire, INSERM U1138, Centre de recherche des Cordeliers, UFR d'Odontologie Garancire, Université Paris Diderot, Paris 75006, France.
³ Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Unité Mixte de Recherche 9196, Centre National de la Recherche Scientifique, Gustave Roussy, Villejuif, 94805, and Université Paris-Sud, Orsay, 91405, France.
⁴ Inserm, U955, Plateforme d'imagerie, Créteil, 9400, France and Université Paris Est, Faculté de médecine, Créteil, 94000, France.

Abstract

Syncytin-A and -B 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. Syncytin-A and -B 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 syncytin-B, SynB^-/- mice, we investigated the potential role of syncytin-B in the fusion of cells from the monocyte/macrophage lineage into multinucleated osteoclasts (OCs) -in bone- or multinucleated giant cells -in soft tissues. In ex vivo 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 syncytin-B expression is maximal in the first 2 days of OC differentiation, argue for syncytin-B playing a role in the fusion of OC and giant cell mononucleated precursors, at initial stages. Finally, ex vivo, 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 syncytin-B is not required for OC activity. In vivo, syncytin-B 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, syncytin-B plays a role in OCs and macrophage fusion; yet it is not essential in vivo for OC and FBGC formation, or maintenance of bone homeostasis, at least under the conditions tested.

Keywords: Cell-cell fusion; Endogenous retrovirus; Envelope gene; Giant cell; Osteoclast; Syncytin.