VEGF-C promotes the development of lymphatics in bone and bone loss

Devon Hominick, Asitha Silva, Noor Khurana, Ying Liu, Paul C. Dechow, Jian Q. Feng, Bronislaw Pytowski, Joseph M. Rutkowski, Kari Alitalo, Michael T. Dellinger

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Patients with Gorham-Stout disease (GSD) have lymphatic vessels in their bones and their bones gradually disappear. Here, we report that mice that overexpress VEGF-C in bone exhibit a phenotype that resembles GSD. To drive VEGF-C expression in bone, we generated Osx-tTA;TetO-Vegfc double-transgenic mice. In contrast to Osx-tTA mice, Osx-tTA;TetO-Vegfc mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics in Osx-tTA;TetO-Vegfc mice. Radiological and histological analysis revealed that bones from Osx-tTA;TetO-Vegfc mice were more porous and had more osteoclasts than bones from Osx-tTA mice. Importantly, we found that bone loss in Osx-tTA; TetO-Vegfc mice could be attenuated by an osteoclast inhibitor. We also discovered that the mutant phenotype of Osx-tTA;TetO-Vegfc mice could be reversed by inhibiting the expression of VEGF-C. Taken together, our results indicate that expression of VEGF-C in bone is sufficient to induce the pathologic hallmarks of GSD in mice.

Original languageEnglish (US)
Article numbere34323
JournaleLife
Volume7
DOIs
StatePublished - Apr 5 2018

Fingerprint

Vascular Endothelial Growth Factor C
Bone
Bone and Bones
Essential Osteolysis
Osteoclasts
Phenotype
Lymphatic Vessels
Osteogenesis
Transgenic Mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Hominick, D., Silva, A., Khurana, N., Liu, Y., Dechow, P. C., Feng, J. Q., ... Dellinger, M. T. (2018). VEGF-C promotes the development of lymphatics in bone and bone loss. eLife, 7, [e34323]. https://doi.org/10.7554/eLife.34323

VEGF-C promotes the development of lymphatics in bone and bone loss. / Hominick, Devon; Silva, Asitha; Khurana, Noor; Liu, Ying; Dechow, Paul C.; Feng, Jian Q.; Pytowski, Bronislaw; Rutkowski, Joseph M.; Alitalo, Kari; Dellinger, Michael T.

In: eLife, Vol. 7, e34323, 05.04.2018.

Research output: Contribution to journalArticle

Hominick, D, Silva, A, Khurana, N, Liu, Y, Dechow, PC, Feng, JQ, Pytowski, B, Rutkowski, JM, Alitalo, K & Dellinger, MT 2018, 'VEGF-C promotes the development of lymphatics in bone and bone loss', eLife, vol. 7, e34323. https://doi.org/10.7554/eLife.34323
Hominick D, Silva A, Khurana N, Liu Y, Dechow PC, Feng JQ et al. VEGF-C promotes the development of lymphatics in bone and bone loss. eLife. 2018 Apr 5;7. e34323. https://doi.org/10.7554/eLife.34323
Hominick, Devon ; Silva, Asitha ; Khurana, Noor ; Liu, Ying ; Dechow, Paul C. ; Feng, Jian Q. ; Pytowski, Bronislaw ; Rutkowski, Joseph M. ; Alitalo, Kari ; Dellinger, Michael T. / VEGF-C promotes the development of lymphatics in bone and bone loss. In: eLife. 2018 ; Vol. 7.
@article{1ac883c8d7d047bbacd3cb2e839c78be,
title = "VEGF-C promotes the development of lymphatics in bone and bone loss",
abstract = "Patients with Gorham-Stout disease (GSD) have lymphatic vessels in their bones and their bones gradually disappear. Here, we report that mice that overexpress VEGF-C in bone exhibit a phenotype that resembles GSD. To drive VEGF-C expression in bone, we generated Osx-tTA;TetO-Vegfc double-transgenic mice. In contrast to Osx-tTA mice, Osx-tTA;TetO-Vegfc mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics in Osx-tTA;TetO-Vegfc mice. Radiological and histological analysis revealed that bones from Osx-tTA;TetO-Vegfc mice were more porous and had more osteoclasts than bones from Osx-tTA mice. Importantly, we found that bone loss in Osx-tTA; TetO-Vegfc mice could be attenuated by an osteoclast inhibitor. We also discovered that the mutant phenotype of Osx-tTA;TetO-Vegfc mice could be reversed by inhibiting the expression of VEGF-C. Taken together, our results indicate that expression of VEGF-C in bone is sufficient to induce the pathologic hallmarks of GSD in mice.",
author = "Devon Hominick and Asitha Silva and Noor Khurana and Ying Liu and Dechow, {Paul C.} and Feng, {Jian Q.} and Bronislaw Pytowski and Rutkowski, {Joseph M.} and Kari Alitalo and Dellinger, {Michael T.}",
year = "2018",
month = "4",
day = "5",
doi = "10.7554/eLife.34323",
language = "English (US)",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - VEGF-C promotes the development of lymphatics in bone and bone loss

AU - Hominick, Devon

AU - Silva, Asitha

AU - Khurana, Noor

AU - Liu, Ying

AU - Dechow, Paul C.

AU - Feng, Jian Q.

AU - Pytowski, Bronislaw

AU - Rutkowski, Joseph M.

AU - Alitalo, Kari

AU - Dellinger, Michael T.

PY - 2018/4/5

Y1 - 2018/4/5

N2 - Patients with Gorham-Stout disease (GSD) have lymphatic vessels in their bones and their bones gradually disappear. Here, we report that mice that overexpress VEGF-C in bone exhibit a phenotype that resembles GSD. To drive VEGF-C expression in bone, we generated Osx-tTA;TetO-Vegfc double-transgenic mice. In contrast to Osx-tTA mice, Osx-tTA;TetO-Vegfc mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics in Osx-tTA;TetO-Vegfc mice. Radiological and histological analysis revealed that bones from Osx-tTA;TetO-Vegfc mice were more porous and had more osteoclasts than bones from Osx-tTA mice. Importantly, we found that bone loss in Osx-tTA; TetO-Vegfc mice could be attenuated by an osteoclast inhibitor. We also discovered that the mutant phenotype of Osx-tTA;TetO-Vegfc mice could be reversed by inhibiting the expression of VEGF-C. Taken together, our results indicate that expression of VEGF-C in bone is sufficient to induce the pathologic hallmarks of GSD in mice.

AB - Patients with Gorham-Stout disease (GSD) have lymphatic vessels in their bones and their bones gradually disappear. Here, we report that mice that overexpress VEGF-C in bone exhibit a phenotype that resembles GSD. To drive VEGF-C expression in bone, we generated Osx-tTA;TetO-Vegfc double-transgenic mice. In contrast to Osx-tTA mice, Osx-tTA;TetO-Vegfc mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics in Osx-tTA;TetO-Vegfc mice. Radiological and histological analysis revealed that bones from Osx-tTA;TetO-Vegfc mice were more porous and had more osteoclasts than bones from Osx-tTA mice. Importantly, we found that bone loss in Osx-tTA; TetO-Vegfc mice could be attenuated by an osteoclast inhibitor. We also discovered that the mutant phenotype of Osx-tTA;TetO-Vegfc mice could be reversed by inhibiting the expression of VEGF-C. Taken together, our results indicate that expression of VEGF-C in bone is sufficient to induce the pathologic hallmarks of GSD in mice.

UR - http://www.scopus.com/inward/record.url?scp=85052002771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052002771&partnerID=8YFLogxK

U2 - 10.7554/eLife.34323

DO - 10.7554/eLife.34323

M3 - Article

C2 - 29620526

AN - SCOPUS:85052002771

VL - 7

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e34323

ER -