Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody...
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doaj-17cd81ff7d3843b595ac6ab978454a8f2021-08-10T07:43:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-08-011210.3389/fgene.2021.705505705505Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta MouseMickaël Cardinal0Antoine Chretien1Thomas Roels2Sébastien Lafont3Michael S. Ominsky4Michael S. Ominsky5Jean-Pierre Devogelaer6Daniel H. Manicourt7Catherine Behets8Pole of Morphology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumPole of Morphology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumPole of Morphology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumPole of Morphology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumRadius Inc., Waltham, MA, United StatesAmgen Inc., Thousand Oaks, CA, United StatesPole of Rheumatic Pathologies, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumPole of Rheumatic Pathologies, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumPole of Morphology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumOsteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout–sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab–treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments.https://www.frontiersin.org/articles/10.3389/fgene.2021.705505/fullosteogenesis imperfectaoim/oimsclerostin antibodyfracturebone qualitybiomechanical strength |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mickaël Cardinal Antoine Chretien Thomas Roels Sébastien Lafont Michael S. Ominsky Michael S. Ominsky Jean-Pierre Devogelaer Daniel H. Manicourt Catherine Behets |
spellingShingle |
Mickaël Cardinal Antoine Chretien Thomas Roels Sébastien Lafont Michael S. Ominsky Michael S. Ominsky Jean-Pierre Devogelaer Daniel H. Manicourt Catherine Behets Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse Frontiers in Genetics osteogenesis imperfecta oim/oim sclerostin antibody fracture bone quality biomechanical strength |
author_facet |
Mickaël Cardinal Antoine Chretien Thomas Roels Sébastien Lafont Michael S. Ominsky Michael S. Ominsky Jean-Pierre Devogelaer Daniel H. Manicourt Catherine Behets |
author_sort |
Mickaël Cardinal |
title |
Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse |
title_short |
Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse |
title_full |
Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse |
title_fullStr |
Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse |
title_full_unstemmed |
Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse |
title_sort |
gender-related impact of sclerostin antibody on bone in the osteogenesis imperfecta mouse |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2021-08-01 |
description |
Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout–sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab–treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments. |
topic |
osteogenesis imperfecta oim/oim sclerostin antibody fracture bone quality biomechanical strength |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2021.705505/full |
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