TY - JOUR
T1 - Targeting vascular endothelial growth factor ameliorates PMMA-particles induced inflammatory osteolysis in murine calvaria
AU - Abu-Amer, Wahid
AU - Arra, Manoj
AU - Clohisy, John C.F.
AU - Abu-Amer, Yousef
AU - Swarnkar, Gaurav
N1 - Funding Information:
This work was supported by NIH/NIAMS R01-AR049192 , R01-AR054326 , R01-AR072623 , (to YA), Biomedical grant # 86200 from Shriners Hospital for Children (YA), and Pilot & Feasibility grant from Washington University Musculoskeletal Research Center NIH P30 AR057235 (to GS).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Inflammation
KW - Osteoclastogenesis
KW - Osteolysis
KW - PMMA
UR - http://www.scopus.com/inward/record.url?scp=85063365757&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2019.03.025
DO - 10.1016/j.bone.2019.03.025
M3 - Article
C2 - 30904629
AN - SCOPUS:85063365757
SN - 8756-3282
VL - 123
SP - 86
EP - 91
JO - Bone
JF - Bone
ER -