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Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9421301/
https://www.ncbi.nlm.nih.gov/pubmed/36046782
http://dx.doi.org/10.3389/fendo.2022.910901
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author 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.
author_facet 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.
author_sort Zamarioli, Ariane
collection PubMed
description 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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spelling pubmed-94213012022-08-30 Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight 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. Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2022-08-15 /pmc/articles/PMC9421301/ /pubmed/36046782 http://dx.doi.org/10.3389/fendo.2022.910901 Text en Copyright © 2022 Zamarioli, Adam, Maupin, Childress, Brinker, Ximenez, Chakraborty, Gautam, Hammamieh and Kacena https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
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.
Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
title Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
title_full Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
title_fullStr Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
title_full_unstemmed Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
title_short Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight
title_sort systemic effects of bmp2 treatment of fractures on non-injured skeletal sites during spaceflight
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9421301/
https://www.ncbi.nlm.nih.gov/pubmed/36046782
http://dx.doi.org/10.3389/fendo.2022.910901
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