Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis

Abstract Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, ske...

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Autores principales:	Masashi Nagao, John L. Hamilton, Ranjan Kc, Agnes D. Berendsen, Xuchen Duan, Chan Wook Cheong, Xin Li, Hee-Jeong Im, Bjorn R. Olsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4517a81285e945cda04564b0bb576f94
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spelling	oai:doaj.org-article:4517a81285e945cda04564b0bb576f942021-12-02T15:04:52ZVascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis10.1038/s41598-017-13417-w2045-2322https://doaj.org/article/4517a81285e945cda04564b0bb576f942017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13417-whttps://doaj.org/toc/2045-2322Abstract Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, skeletal growth and postnatal homeostasis. This raises questions of how the important embryonic and postnatal functions of VEGF can be reconciled with an apparently destructive role in OA. Addressing these questions, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.Masashi NagaoJohn L. HamiltonRanjan KcAgnes D. BerendsenXuchen DuanChan Wook CheongXin LiHee-Jeong ImBjorn R. OlsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masashi Nagao John L. Hamilton Ranjan Kc Agnes D. Berendsen Xuchen Duan Chan Wook Cheong Xin Li Hee-Jeong Im Bjorn R. Olsen Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis
description	Abstract Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, skeletal growth and postnatal homeostasis. This raises questions of how the important embryonic and postnatal functions of VEGF can be reconciled with an apparently destructive role in OA. Addressing these questions, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.
format	article
author	Masashi Nagao John L. Hamilton Ranjan Kc Agnes D. Berendsen Xuchen Duan Chan Wook Cheong Xin Li Hee-Jeong Im Bjorn R. Olsen
author_facet	Masashi Nagao John L. Hamilton Ranjan Kc Agnes D. Berendsen Xuchen Duan Chan Wook Cheong Xin Li Hee-Jeong Im Bjorn R. Olsen
author_sort	Masashi Nagao
title	Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis
title_short	Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis
title_full	Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis
title_fullStr	Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis
title_full_unstemmed	Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis
title_sort	vascular endothelial growth factor in cartilage development and osteoarthritis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4517a81285e945cda04564b0bb576f94
work_keys_str_mv	AT masashinagao vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT johnlhamilton vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT ranjankc vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT agnesdberendsen vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT xuchenduan vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT chanwookcheong vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT xinli vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT heejeongim vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis AT bjornrolsen vascularendothelialgrowthfactorincartilagedevelopmentandosteoarthritis
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Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis

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