Dissecting the mechanisms of bone loss in Gorham-Stout disease

Rossi, Michela; Buonuomo, Paola Sabrina; Battafarano, Giulia; Conforti, Antonella; Mariani, Eda; Algeri, Mattia; Pelle, Simone; D’Agostini, Matteo; Macchiaiolo, Marina; De Vito, Rita; Gonfiantini, Michaela Veronika; Jenkner, Alessandro; Rana, Ippolita; Bartuli, Andrea; Del Fattore, Andrea

Affiliations

¹Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children’s Hospital, Rome, Italy

²Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, Rome, Italy

³Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, Italy

⁴Research Laboratories, Bambino Gesù Children's Hospital, Rome, Italy

⁵Villa Aurora” Clinic, Rome, Italy

⁶Histopathology, Bambino Gesù Children's Hospital, Rome, Italy

⁷Division of Immunology and Infectious Diseases Department of Pediatrics, Bambino Gesù Children Hospital, Rome, Italy

Abstract and keywords

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.

Keywords: Gorham-Stout disease; Osteolysis; Osteoclast; Bone histomorphometry; Osteoblast

Links

DOI: 10.1016/j.bone.2019.115068

PubMed: 31525474

WoS: 000503321100027

History

Received: 2019-07-01

Revised: 2019-09-11

Accepted: 2019-09-11

Online: 2019-09-13

Cited Works (6)

Year	Entry
2008	Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. September 2008;83(9):1032-1045.
1969	Bélanger LF. Osteocytic osteolysis. Calcif Tiss Res. December 1969;4(1):1-12.
2006	Nicolella DP, Moravits DE, Gale AM, Bonewald LF, Lankford J. Osteocyte lacunae tissue strain in cortical bone. J Biomech. 2006;39(9):1735-1743.
2013	Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM. Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. January 2013;28(1):2-17.
2003	Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. January 2003;22(23):6267-6276.
2012	Tang SY, Herber R-P, Ho SP, Alliston T. Matrix metalloproteinase–13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance. J Bone Miner Res. September 2012;27(9):1936-1950.

Cited By (1)

Year	Entry
2022	Pepe J, Rossi M, Battafarano G, Vernocchi P, Conte F, Marzano V, Mariani E, Mortera SL, Cipriani C, Rana I, Buonuomo PS, Bartuli A, De Martino V, Pelle S, Pascucci L, Toniolo RM, Putignani L, Minisola S, Fattore AD. Characterization of extracellular vesicles in osteoporotic patients compared to osteopenic and healthy controls. J Bone Miner Res. November 2022;37(11):2186-2200.