Lymphatics in bone arise from pre-existing lymphatics

被引：22

作者：

Monroy, Marco ^{[1
,2
]}

McCarter, Anna L. ^{[1
,2
]}

Hominick, Devon ^{[1
,2
]}

Cassidy, Nina ^{[1
,2
]}

Dellinger, Michael T. ^{[1
,2
,3
,4
]}

机构：

[1] UT Southwestern Med Ctr, Dept Surg, Div Surg Oncol, Dallas, TX 75390 USA

[2] UT Southwestern Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA

[3] UT Southwestern Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA

[4] UT Southwestern Med Ctr, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA

来源：

DEVELOPMENT | 2020年 / 147卷 / 21期

基金：

美国国家卫生研究院;

关键词：

Gorham-Stout disease; Generalized lymphatic anomaly; VEGF-C; PIK3CA; Rapamycin; ENDOTHELIAL-CELLS; HEMOGENIC ENDOTHELIUM; GROWTH-FACTOR; SIROLIMUS; OSTEOPETROSIS; CONTRIBUTE; MUTATIONS; PHENOTYPE; ORIGIN; GENE;

D O I：

10.1242/dev.184291

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Proxl -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.

引用

页数：14

共 36 条

[31] Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature [J].