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

VEGF-C promotes the development of lymphatics in bone and bone loss.
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Hominick D, Silva A, Khurana N, Liu Y, Dechow PC, Feng JQ, Pytowski B, Rutkowski JM, Alitalo K, Dellinger MT,


Hominick D, Silva A, Khurana N, Liu Y, Dechow PC, Feng JQ, Pytowski B, Rutkowski JM, Alitalo K, Dellinger MT, (click to view)

Hominick D, Silva A, Khurana N, Liu Y, Dechow PC, Feng JQ, Pytowski B, Rutkowski JM, Alitalo K, Dellinger MT,

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eLife 2018 04 057() doi 10.7554/eLife.34323

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 generateddouble-transgenic mice. In contrast tomice,mice developed lymphatics in their bones. We found that inhibition of VEGFR3, but not VEGFR2, prevented the formation of bone lymphatics inmice. Radiological and histological analysis revealed that bones frommice were more porous and had more osteoclasts than bones frommice. Importantly, we found that bone loss inmice could be attenuated by an osteoclast inhibitor. We also discovered that the mutant phenotype ofmice 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.

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