Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect

Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect

Abstract Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported...

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Main Authors: Shaoyi Wang, Mengyu Li, Wenjie Zhang, Hongfei Hua, Ningtao Wang, Jun Zhao, Jing Ge, Xinquan Jiang, Zhiyuan Zhang, Dongxia Ye, Chi Yang
Format: Article
Language:English
Published: Nature Publishing Group 2017-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-09210-4
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spelling doaj-9d99abbf26ed406ba639ac350c4555e32020-12-08T01:23:54ZengNature Publishing GroupScientific Reports2045-23222017-08-017111210.1038/s41598-017-09210-4Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defectShaoyi Wang0Mengyu Li1Wenjie Zhang2Hongfei Hua3Ningtao Wang4Jun Zhao5Jing Ge6Xinquan Jiang7Zhiyuan Zhang8Dongxia Ye9Chi Yang10Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Prosthodontics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Orthodontics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Prosthodontics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyShanghai Research Institute of Stomatology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyDepartment of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of StomatologyAbstract Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported to be a potential angiogenic cytokine and has an ability to promote the proliferation of human umbilical vein endothelial cells(HUVECs). Whether it can be applied for promoting vascularized bone regeneration is still unknown. In this study, we demonstrated that GDF15 augmented the expression of cyclins D1 and E, induced Rb phosphorylation and E2F-1 nuclear translocation, as well as increased HUVECs proliferation. Furthermore, we also observed that GDF15 promoted the formation of functional vessels at an artificially-induced angiogenic site, and remarkably improved the healing in the repair of critical-sized calvarial defects. Our results confirm the essential role of GDF15 in angiogenesis and suggest its potential beneficial use in regenerative medicine.https://doi.org/10.1038/s41598-017-09210-4
collection DOAJ
language English
format Article
sources DOAJ
author Shaoyi Wang
Mengyu Li
Wenjie Zhang
Hongfei Hua
Ningtao Wang
Jun Zhao
Jing Ge
Xinquan Jiang
Zhiyuan Zhang
Dongxia Ye
Chi Yang
spellingShingle Shaoyi Wang
Mengyu Li
Wenjie Zhang
Hongfei Hua
Ningtao Wang
Jun Zhao
Jing Ge
Xinquan Jiang
Zhiyuan Zhang
Dongxia Ye
Chi Yang
Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
Scientific Reports
author_facet Shaoyi Wang
Mengyu Li
Wenjie Zhang
Hongfei Hua
Ningtao Wang
Jun Zhao
Jing Ge
Xinquan Jiang
Zhiyuan Zhang
Dongxia Ye
Chi Yang
author_sort Shaoyi Wang
title Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
title_short Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
title_full Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
title_fullStr Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
title_full_unstemmed Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
title_sort growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-08-01
description Abstract Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported to be a potential angiogenic cytokine and has an ability to promote the proliferation of human umbilical vein endothelial cells(HUVECs). Whether it can be applied for promoting vascularized bone regeneration is still unknown. In this study, we demonstrated that GDF15 augmented the expression of cyclins D1 and E, induced Rb phosphorylation and E2F-1 nuclear translocation, as well as increased HUVECs proliferation. Furthermore, we also observed that GDF15 promoted the formation of functional vessels at an artificially-induced angiogenic site, and remarkably improved the healing in the repair of critical-sized calvarial defects. Our results confirm the essential role of GDF15 in angiogenesis and suggest its potential beneficial use in regenerative medicine.
url https://doi.org/10.1038/s41598-017-09210-4
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