The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice

被引:7
|
作者
Dadwal, Ushashi C. [1 ,2 ]
Bhatti, Fazal Ur Rehman [1 ,2 ]
Awosanya, Olatundun D. [1 ]
Nagaraj, Rohit U. [1 ]
Perugini, Anthony J. [1 ]
Sun, Seungyup [1 ]
Valuch, Conner R. [3 ]
Staut, Caio de Andrade [1 ]
Mendenhall, Stephen K. [1 ]
Tewari, Nikhil P. [1 ]
Mostardo, Sarah L. [1 ]
Nazzal, Murad K. [1 ]
Battina, Hanisha L. [1 ]
Zhou, Donghui [1 ]
Kanagasabapathy, Deepa [1 ]
Blosser, Rachel J. [1 ,2 ]
Mulcrone, Patrick L. [4 ]
Li, Jiliang [3 ]
Kacena, Melissa A. [1 ,2 ]
机构
[1] Indiana Univ Sch Med, Dept Orthopaed Surg, 1130 W Michigan St,FH 115, Indianapolis, IN 46202 USA
[2] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA
[3] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46205 USA
[4] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA
来源
FASEB JOURNAL | 2021年 / 35卷 / 09期
基金
美国国家科学基金会;
关键词
aging; bone morphogenetic protein; endothelial cells; sex-based differences; thrombopoietin; FRACTURE; EXPRESSION; VASCULARIZATION; ANGIOPOIETIN-1; SENESCENCE; MORTALITY; STEM;
D O I
10.1096/fj.202001616RR
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.
引用
收藏
页数:16
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