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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
Author(s) -
Dadwal Ushashi C.,
Bhatti Fazal Ur Rehman,
Awosanya Olatundun D.,
Nagaraj Rohit U.,
Perugini Anthony J.,
Sun Seungyup,
Valuch Conner R.,
Andrade Staut Caio,
Mendenhall Stephen K.,
Tewari Nikhil P.,
Mostardo Sarah L.,
Nazzal Murad K.,
Battina Hanisha L.,
Zhou Donghui,
Kanagasabapathy Deepa,
Blosser Rachel J.,
Mulcrone Patrick L.,
Li Jiliang,
Kacena Melissa A.
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001616rr
Subject(s) - angiogenesis , thrombopoietin , bone healing , bone marrow , cd31 , bone morphogenetic protein 2 , bone morphogenetic protein , vascular endothelial growth factor , endothelial progenitor cell , medicine , endothelial stem cell , endocrinology , immunology , cancer research , progenitor cell , microbiology and biotechnology , chemistry , biology , stem cell , in vitro , haematopoiesis , anatomy , gene , biochemistry , vegf receptors
Abstract 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.