Coudert Amélie E, Redelsperger François, Chabbi-Achengli Yasmine, Vernochet Cécile, Marty Caroline, Decrouy Xavier, Heidmann Thierry, de Vernejoul Marie-Christine, Dupressoir Anne
BIOSCAR, Unité Mixte de Recherche 1132, Institut National de la Santé et de la Recherche Médicale, Hôpital Lariboisière, Paris 75010, France.
Laboratoire de Physiopathologie Orale Moléculaire, INSERM U1138, Centre de recherche des Cordeliers, UFR d'Odontologie Garancire, Université Paris Diderot, Paris 75006, France.
Bone Rep. 2019 Jul 10;11:100214. doi: 10.1016/j.bonr.2019.100214. eCollection 2019 Dec.
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.
和是逆转录病毒起源的包膜基因，在进化过程中被捕获，在胎盘形成中发挥作用。它们触发细胞间融合，并被证明在小鼠胎盘形成过程中对合体滋养层的形成至关重要。和的表达已在其他组织中被描述，其高度融合的特性表明它们可能参与其他细胞类型的融合。在这里，利用敲除的小鼠（SynB小鼠），我们研究了在单核细胞/巨噬细胞谱系的细胞融合形成多核破骨细胞（OCs）（在骨中）或多核巨细胞（在软组织中）中的潜在作用。在实验中，与野生型细胞培养相比，在SynB小鼠中，早在第3天就观察到融合指数以及多核OCs和巨细胞数量显著减少。有趣的是，每个多核OC或巨细胞的核数量保持不变。这些结果，连同证明在OC分化的前2天表达最高，表明在初始阶段在OC和巨细胞单核前体的融合中发挥作用。最后，观察到的多核OC数量减少对OC分化标志物的表达没有影响，并且牙本质吸收试验没有证明破骨细胞吸收活性有任何差异，这表明OC活性不需要。此外，发现在胚胎第16.5天在胚胎的骨膜中表达，在那里观察到TRAP阳性细胞。然而，在成年小鼠中，在SynB小鼠中未观察到OC数量显著减少或骨表型改变。此外，与野生型小鼠相比，SynB小鼠在对异物植入形成的异物巨细胞（FBGCs）数量上没有显示任何变化。总之，结果表明，除了在胎盘形成中的重要作用外，在OCs和巨噬细胞融合中发挥作用；然而，至少在所测试的条件下，对于OC和FBGC的形成或骨稳态的维持不是必需的。
