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Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to impr...

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Autores principales: Conrad, Kirk P., Phillips, Ean G., Jiron, Jessica, Bailes, Julie, Dhar, Biswadeep, Diao, YanPeng, Aguirre, Jose Ignacio, Yarrow, Joshua F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545299/
https://www.ncbi.nlm.nih.gov/pubmed/31155858
http://dx.doi.org/10.14814/phy2.14106
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author Conrad, Kirk P.
Phillips, Ean G.
Jiron, Jessica
Bailes, Julie
Dhar, Biswadeep
Diao, YanPeng
Aguirre, Jose Ignacio
Yarrow, Joshua F.
author_facet Conrad, Kirk P.
Phillips, Ean G.
Jiron, Jessica
Bailes, Julie
Dhar, Biswadeep
Diao, YanPeng
Aguirre, Jose Ignacio
Yarrow, Joshua F.
author_sort Conrad, Kirk P.
collection PubMed
description Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to improve osseous blood flow, thereby accelerating bone fracture closure. Relaxin is secreted by the ovary and circulates in rodents and humans during pregnancy. Because relaxin might benefit bone fracture healing by stimulating angiogenesis, vasculogenesis (and potentially osteogenesis) through mobilization and activation of bone marrow progenitor cells, and by increasing blood flow via vasodilation, we investigated whether relaxin administration would accelerate closure of a calvarial defect in mice. Whether administered systemically by osmotic pump or locally by collagen scaffolds for ~2 week period after lesioning, relaxin did not accelerate bone healing. Despite implementing relaxin doses that reached plasma concentrations spanning the physiological to supraphysiological range, testing the closure of two different sizes of calvarial lesions, allowing for different intervals of time from instigation of cranial lesion to euthanasia, and investigating mice of different ages, we did not observe a significant benefit of relaxin in bone lesion healing. Nor did we observe stimulation of blood vessel formation in the bone lesion by the hormone. An incidental finding was that relaxin appeared to enhance trabecular bone growth in an uninjured control bone (femur). Although the results of this study were not supportive of a therapeutic benefit for relaxin on calvarial defect closure, future investigation is needed employing different animal species and experimental models of bone fracture.
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spelling pubmed-65452992019-06-05 Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice Conrad, Kirk P. Phillips, Ean G. Jiron, Jessica Bailes, Julie Dhar, Biswadeep Diao, YanPeng Aguirre, Jose Ignacio Yarrow, Joshua F. Physiol Rep Original Research Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to improve osseous blood flow, thereby accelerating bone fracture closure. Relaxin is secreted by the ovary and circulates in rodents and humans during pregnancy. Because relaxin might benefit bone fracture healing by stimulating angiogenesis, vasculogenesis (and potentially osteogenesis) through mobilization and activation of bone marrow progenitor cells, and by increasing blood flow via vasodilation, we investigated whether relaxin administration would accelerate closure of a calvarial defect in mice. Whether administered systemically by osmotic pump or locally by collagen scaffolds for ~2 week period after lesioning, relaxin did not accelerate bone healing. Despite implementing relaxin doses that reached plasma concentrations spanning the physiological to supraphysiological range, testing the closure of two different sizes of calvarial lesions, allowing for different intervals of time from instigation of cranial lesion to euthanasia, and investigating mice of different ages, we did not observe a significant benefit of relaxin in bone lesion healing. Nor did we observe stimulation of blood vessel formation in the bone lesion by the hormone. An incidental finding was that relaxin appeared to enhance trabecular bone growth in an uninjured control bone (femur). Although the results of this study were not supportive of a therapeutic benefit for relaxin on calvarial defect closure, future investigation is needed employing different animal species and experimental models of bone fracture. John Wiley and Sons Inc. 2019-06-02 /pmc/articles/PMC6545299/ /pubmed/31155858 http://dx.doi.org/10.14814/phy2.14106 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Conrad, Kirk P.
Phillips, Ean G.
Jiron, Jessica
Bailes, Julie
Dhar, Biswadeep
Diao, YanPeng
Aguirre, Jose Ignacio
Yarrow, Joshua F.
Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
title Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
title_full Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
title_fullStr Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
title_full_unstemmed Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
title_short Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
title_sort potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545299/
https://www.ncbi.nlm.nih.gov/pubmed/31155858
http://dx.doi.org/10.14814/phy2.14106
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