Browsing by Subject "Bone morphogenetic protein"

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    Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
    (Frontiers Media, 2022-08-15) Zamarioli, Ariane; Adam, Gremah; Maupin, Kevin A.; Childress, Paul J.; Brinker, Alexander; Ximenez, Joao P. B.; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    Unloading associated with spaceflight results in bone loss and increased fracture risk. Bone morphogenetic protein 2 (BMP2) is known to enhance bone formation, in part, through molecular pathways associated with mechanical loading; however, the effects of BMP2 during spaceflight remain unclear. Here, we investigated the systemic effects of BMP2 on mice sustaining a femoral fracture followed by housing in spaceflight (International Space Station or ISS) or on Earth. We hypothesized that in spaceflight, the systemic effects of BMP2 on weight-bearing bones would be blunted compared to that observed on Earth. Nine-week-old male mice were divided into four groups: 1) Saline+Earth; 2) BMP+Earth; 3) Saline+ISS; and 4) BMP+ISS (n = 10 mice/group, but only n = 5 mice/group were reserved for micro-computed tomography analyses). All mice underwent femoral defect surgery and were followed for approximately 4 weeks. We found a significant reduction in trabecular separation within the lumbar vertebrae after administering BMP2 at the fracture site of mice housed on Earth. In contrast, BMP2 treatment led to a significant increase in trabecular separation concomitant with a reduction in trabecular number within spaceflown tibiae. Although these and other lines of evidence support our hypothesis, the small sample size associated with rodent spaceflight studies limits interpretations. That said, it appears that a locally applied single dose of BMP2 at the femoral fracture site can have a systemic impact on distant bones, affecting bone quantity in several skeletal sites. Moreover, our results suggest that BMP2 treatment works through a pathway involving mechanical loading in which the best outcomes during its treatment on Earth occurred in the weight-bearing bones and in spaceflight occurred in bones subjected to higher muscle contraction.
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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
    (Wiley, 2021) Dadwal, Ushashi C.; Bhatti, Fazal Ur Rehman; Awosanya, Olatundun D.; Nagaraj, Rohit U.; Perugini, Anthony J., III.; Sun, Seungyup; Valuch, Conner R.; Staut, Caio de Andrade; 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.; Orthopaedic Surgery, School of Medicine
    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.