Dissecting the mechanisms of bone loss in Gorham-Stout disease

Research output: Contribution to journalArticle

Abstract

Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients' bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients' sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.

Original languageEnglish
Pages (from-to)115068
JournalBone
DOIs
Publication statusE-pub ahead of print - Sep 13 2019

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Essential Osteolysis
Bone and Bones
Osteoclasts
Serum
Osteoblasts
Osteocytes
Osteolysis
Bone Resorption
Osteogenesis
Vascular Endothelial Growth Factor A
Interleukin-6
Endothelial Cells
Biopsy

Cite this

@article{c04340b3ef2140dbb5048c55919448af,
title = "Dissecting the mechanisms of bone loss in Gorham-Stout disease",
abstract = "Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients' bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients' sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.",
author = "Michela Rossi and Buonuomo, {Paola Sabrina} and Giulia Battafarano and Antonella Conforti and Eda Mariani and Mattia Algeri and Simone Pelle and Matteo D'Agostini and Marina Macchiaiolo and {De Vito}, Rita and Gonfiantini, {Michaela Veronika} and Alessandro Jenkner and Ippolita Rana and Andrea Bartuli and {Del Fattore}, Andrea",
note = "Copyright {\circledC} 2018. Published by Elsevier Inc.",
year = "2019",
month = "9",
day = "13",
doi = "10.1016/j.bone.2019.115068",
language = "English",
pages = "115068",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Dissecting the mechanisms of bone loss in Gorham-Stout disease

AU - Rossi, Michela

AU - Buonuomo, Paola Sabrina

AU - Battafarano, Giulia

AU - Conforti, Antonella

AU - Mariani, Eda

AU - Algeri, Mattia

AU - Pelle, Simone

AU - D'Agostini, Matteo

AU - Macchiaiolo, Marina

AU - De Vito, Rita

AU - Gonfiantini, Michaela Veronika

AU - Jenkner, Alessandro

AU - Rana, Ippolita

AU - Bartuli, Andrea

AU - Del Fattore, Andrea

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2019/9/13

Y1 - 2019/9/13

N2 - Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients' bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients' sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.

AB - Gorham-Stout disease (GSD) is a rare disorder characterized by progressive osteolysis and angiomatous proliferation. Since the mechanisms leading to bone loss in GSD are not completely understood, we performed histological, serum, cellular and molecular analyses of 7 patients. Increased vessels, osteoclast number and osteocyte lacunar area were revealed in patients' bone biopsies. Biochemical analysis of sera showed high levels of ICTP, Sclerostin, VEGF-A and IL-6. In vitro experiments revealed increased osteoclast differentiation and activity, and impaired mineralization ability of osteoblasts. To evaluate the involvement of systemic factors in GSD, control cells were treated with patients' sera and displayed an increase of osteoclastogenesis, bone resorption activity and a reduction of osteoblast function. Interestingly, GSD sera stimulated the vessel formation by endothelial cells EA.hy926. These results suggest that bone cell autonomous alterations with the cooperation of systemic factors are involved in massive bone loss and angiomatous proliferation observed in GSD patients.

U2 - 10.1016/j.bone.2019.115068

DO - 10.1016/j.bone.2019.115068

M3 - Article

C2 - 31525474

SP - 115068

JO - Bone

JF - Bone

SN - 8756-3282

ER -