Division of Surgical Oncology, Department of Surgery and The Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Division of Surgical Oncology, Department of Surgery and The Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USA
Development. 2020 Apr 20;147(21):dev184291. doi: 10.1242/dev.184291.
Bones do not normally have lymphatics. However, individuals with generalized lymphatic anomaly (GLA) or Gorham-Stout disease (GSD) develop ectopic lymphatics in bone. Despite growing interest in the development of tissue-specific lymphatics, the cellular origin of bone lymphatic endothelial cells (bLECs) is not known and the development of bone lymphatics has not been fully characterized. Here, we describe the development of bone lymphatics in mouse models of GLA and GSD. Through lineage-tracing experiments, we show that bLECs arise from pre-existing Prox1-positive LECs. We show that bone lymphatics develop in a stepwise manner where regional lymphatics grow, breach the periosteum and then invade bone. We also show that the development of bone lymphatics is impaired in mice that lack osteoclasts. Last, we show that rapamycin can suppress the growth of bone lymphatics in our models of GLA and GSD. In summary, we show that bLECs can arise from pre-existing LECs and that rapamycin can prevent the growth of bone lymphatics.
骨骼通常没有淋巴管。然而，患有全身性淋巴管异常（GLA）或 Gorham-Stout 病（GSD）的个体在骨骼中会发育出异位淋巴管。尽管人们对组织特异性淋巴管的发育越来越感兴趣，但骨骼淋巴管内皮细胞（bLEC）的细胞起源尚不清楚，骨骼淋巴管的发育也尚未完全阐明。在这里，我们描述了 GLA 和 GSD 小鼠模型中骨骼淋巴管的发育。通过谱系追踪实验，我们表明 bLEC 源自先前存在的 Prox1 阳性 LEC。我们表明，骨骼淋巴管的发育是分阶段进行的，区域性淋巴管生长、突破骨膜，然后侵入骨骼。我们还表明，缺乏破骨细胞的小鼠骨骼淋巴管的发育受损。最后，我们表明雷帕霉素可以抑制我们 GLA 和 GSD 模型中骨骼淋巴管的生长。总之，我们表明 bLEC 可以起源于先前存在的 LEC，并且雷帕霉素可以阻止骨骼淋巴管的生长。
