Targeting vascular endothelial growth factor ameliorates PMMA-particles induced inflammatory osteolysis in murine calvaria.
Angiogenesis
Inflammation
Osteoclastogenesis
Osteolysis
PMMA
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
08
01
2019
revised:
07
03
2019
accepted:
19
03
2019
pubmed:
25
3
2019
medline:
7
7
2020
entrez:
25
3
2019
Statut:
ppublish
Résumé
Cytokines and growth factors mediate inflammatory osteolysis in response to particles released from bone implants. However, the mechanism by which this process develops is not entirely clear. Blood vessels and related factors may be required to deliver immune cells and soluble factors to the injury site. Therefore, in the current study we investigated if, vascular endothelial growth factor (VEGF), which is required for angiogenesis, mediates polymethylmethacrylate (PMMA) particles-induced osteolysis. Using bone marrow derived macrophages (BMMs) and ST2 stromal cell line, we show that PMMA particles increase VEGF expression. Further, using a murine calvarial osteolysis model, we found that PMMA injection over calvaria induce significant increase in VEGF expression as well as new vessel formation, represented by von Willebrand factor (vWF) staining. Co-treatment using a VEGF-neutralizing antibody abrogated expression of vWF, indicating decreased angiogenesis. Finally, VEGF neutralizing antibody reduced expression of Tumor necrosis factor (TNF) and decreased osteoclastogenesis induced by PMMA particles in calvariae. This work highlights the significance of angiogenesis, specifically VEGF, as key driver of PMMA particle-induced inflammatory osteolysis, inhibition of which attenuates this response.
Identifiants
pubmed: 30904629
pii: S8756-3282(19)30109-7
doi: 10.1016/j.bone.2019.03.025
pmc: PMC6491226
mid: NIHMS1525642
pii:
doi:
Substances chimiques
Bone Cements
0
Vascular Endothelial Growth Factor A
0
vascular endothelial growth factor A, mouse
0
Polymethyl Methacrylate
9011-14-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
86-91Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR072623
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR049192
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007200
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR057235
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR054326
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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