The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing

Dong Wang,1 Jingyi Wang,2 Junlin Zhou,1 Xi Zheng2 1Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of SICU, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wang D, Wang J, Zhou J, Zheng X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	adenosine a2a receptor angiogenesis vascular endothelial cells macrophages bone healing Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b6d847ef4c5d494b81a755c69ca0c415
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b6d847ef4c5d494b81a755c69ca0c415
record_format	dspace
spelling	oai:doaj.org-article:b6d847ef4c5d494b81a755c69ca0c4152021-12-02T16:45:31ZThe Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing1178-7031https://doaj.org/article/b6d847ef4c5d494b81a755c69ca0c4152021-08-01T00:00:00Zhttps://www.dovepress.com/the-role-of-adenosine-receptor-a2a-in-the-regulation-of-macrophage-exo-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Dong Wang,1 Jingyi Wang,2 Junlin Zhou,1 Xi Zheng2 1Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of SICU, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xi ZhengDepartment of SICU, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaEmail xizheng_article@outlook.comBackground: Macrophage exosomes and vascular endothelial cells (VECs) are critical to bone healing. However, few studies explore the molecular regulation of them in the bone fracture microenvironment.Methods: In this study, we explored the effects of adenosine receptor A2A (ADA2AR) in macrophage exosomes and VECs during bone healing. CGS21680 (an ADA2AR agonist) and ZM241385 (an ADA2AR antagonist) were used. First, the effects of the ADA2AR on VECs during bone healing were studied in vivo in a rat tibial fracture model. Second, the effects of ADA2AR on VECs and in the regulation of VECs by macrophages were examined in the bone fracture microenvironment. Third, the effects of ADA2AR on the regulation of macrophage exosomes on VECs were analyzed. Finally, the genes and long non-coding RNAs (lncRNAs) associated with the regulation of VECs by the ADA2AR were examined by high-throughput sequencing and bioinformatics analysis.Results: CGS21680 accelerated VEC proliferation in the early stage of bone healing and that ZM241385 suppressed VEC proliferation in vivo. ZM241385 inhibited cell viability and tube formation in vitro. However, CGS21680 did not promote tube formation, cell proliferation, or cell migration in vitro. The inhibition of macrophage exosomes could suppress tube formation and VEC migration. CGS21680 had no effects on tube formation in a macrophage-VEC co-culture. The macrophage exosomes were purified and CGS21680 promoted the macrophage secretion of exosomes. In contrast, ZM241385 inhibited the macrophage secretion exosomes. Finally, the lncRNA and mRNA involved in the activation of the ADA2AR in VECs were analyzed. CGS21680 upregulated 3274 mRNAs and downregulated 2236 mRNAs, and upregulated 1696 lncRNAs and downregulated 1882 lncRNAs. The hub genes involved in angiogenesis were Flt1, Fgf2, Mapk14, Fn1, and Jun.Conclusion: The activation of ADA2AR was essential for angiogenesis and the secretion of exosomes by macrophages during bone healing; moreover, the inactivation of the ADA2AR led to poor angiogenesis and bone nonunion.Keywords: adenosine A2A receptor, angiogenesis, vascular endothelial cells, macrophages, bone healingWang DWang JZhou JZheng XDove Medical Pressarticleadenosine a2a receptorangiogenesisvascular endothelial cellsmacrophagesbone healingPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4001-4017 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adenosine a2a receptor angiogenesis vascular endothelial cells macrophages bone healing Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	adenosine a2a receptor angiogenesis vascular endothelial cells macrophages bone healing Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Wang D Wang J Zhou J Zheng X The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing
description	Dong Wang,1 Jingyi Wang,2 Junlin Zhou,1 Xi Zheng2 1Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of SICU, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xi ZhengDepartment of SICU, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaEmail xizheng_article@outlook.comBackground: Macrophage exosomes and vascular endothelial cells (VECs) are critical to bone healing. However, few studies explore the molecular regulation of them in the bone fracture microenvironment.Methods: In this study, we explored the effects of adenosine receptor A2A (ADA2AR) in macrophage exosomes and VECs during bone healing. CGS21680 (an ADA2AR agonist) and ZM241385 (an ADA2AR antagonist) were used. First, the effects of the ADA2AR on VECs during bone healing were studied in vivo in a rat tibial fracture model. Second, the effects of ADA2AR on VECs and in the regulation of VECs by macrophages were examined in the bone fracture microenvironment. Third, the effects of ADA2AR on the regulation of macrophage exosomes on VECs were analyzed. Finally, the genes and long non-coding RNAs (lncRNAs) associated with the regulation of VECs by the ADA2AR were examined by high-throughput sequencing and bioinformatics analysis.Results: CGS21680 accelerated VEC proliferation in the early stage of bone healing and that ZM241385 suppressed VEC proliferation in vivo. ZM241385 inhibited cell viability and tube formation in vitro. However, CGS21680 did not promote tube formation, cell proliferation, or cell migration in vitro. The inhibition of macrophage exosomes could suppress tube formation and VEC migration. CGS21680 had no effects on tube formation in a macrophage-VEC co-culture. The macrophage exosomes were purified and CGS21680 promoted the macrophage secretion of exosomes. In contrast, ZM241385 inhibited the macrophage secretion exosomes. Finally, the lncRNA and mRNA involved in the activation of the ADA2AR in VECs were analyzed. CGS21680 upregulated 3274 mRNAs and downregulated 2236 mRNAs, and upregulated 1696 lncRNAs and downregulated 1882 lncRNAs. The hub genes involved in angiogenesis were Flt1, Fgf2, Mapk14, Fn1, and Jun.Conclusion: The activation of ADA2AR was essential for angiogenesis and the secretion of exosomes by macrophages during bone healing; moreover, the inactivation of the ADA2AR led to poor angiogenesis and bone nonunion.Keywords: adenosine A2A receptor, angiogenesis, vascular endothelial cells, macrophages, bone healing
format	article
author	Wang D Wang J Zhou J Zheng X
author_facet	Wang D Wang J Zhou J Zheng X
author_sort	Wang D
title	The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing
title_short	The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing
title_full	The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing
title_fullStr	The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing
title_full_unstemmed	The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing
title_sort	role of adenosine receptor a2a in the regulation of macrophage exosomes and vascular endothelial cells during bone healing
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b6d847ef4c5d494b81a755c69ca0c415
work_keys_str_mv	AT wangd theroleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT wangj theroleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT zhouj theroleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT zhengx theroleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT wangd roleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT wangj roleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT zhouj roleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing AT zhengx roleofadenosinereceptora2aintheregulationofmacrophageexosomesandvascularendothelialcellsduringbonehealing
_version_	1718383476401504256

The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing

Ejemplares similares