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The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice

BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function....

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Autores principales: Patoine, Alexa, Husseini, Abdallah, Kasaai, Bahar, Gaumond, Marie-Hélène, Moffatt, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589259/
https://www.ncbi.nlm.nih.gov/pubmed/28880886
http://dx.doi.org/10.1371/journal.pone.0184568
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author Patoine, Alexa
Husseini, Abdallah
Kasaai, Bahar
Gaumond, Marie-Hélène
Moffatt, Pierre
author_facet Patoine, Alexa
Husseini, Abdallah
Kasaai, Bahar
Gaumond, Marie-Hélène
Moffatt, Pierre
author_sort Patoine, Alexa
collection PubMed
description BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function. Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene. Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood. A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems. Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model. KO mice reproduced and thrived normally up to 12 month of age. The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points. Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies. Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders. These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test. In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin). Gene expression monitoring also revealed no major impact of the loss of BRIL. Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT. Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium. In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL.
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spelling pubmed-55892592017-09-15 The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice Patoine, Alexa Husseini, Abdallah Kasaai, Bahar Gaumond, Marie-Hélène Moffatt, Pierre PLoS One Research Article BRIL (bone-restricted IFITM-like), is a short transmembrane protein expressed almost exclusively in osteoblasts. Although much is known about its bone-restricted gene expression pattern and protein biochemical and topological features, little information is available for BRIL physiological function. Two autosomal dominant forms of osteogenesis imperfecta (OI) are caused by distinct, but recurrent mutations in the BRIL gene. Yet, the underlying mechanisms by which those mutations lead to OI are still poorly understood. A previous report indicated that BRIL knockout (KO) mice had bone deformities, shortened long bones, and reproductive problems. Here we generated and systematically analyzed the skeletal phenotype of a new global Bril KO/LacZ knockin mouse model. KO mice reproduced and thrived normally up to 12 month of age. The skeletal phenotype of KO and WT littermates was assessed at embryonic (E13.5 to E18.5) and postnatal (2 days, 3 weeks, 3 months and 8 months) time-points. Embryos from E13.5 through to E18.5 showed significant X-Gal staining in all skeletal elements without any apparent patterning anomalies. Although bone deformities were never observed at any postnatal ages, minor and transient differences were noted in terms of bone length and static uCT parameters, but not systematically across all ages and genders. These changes, however, were not accompanied by significant alteration in bone material properties as assessed by a 3-point bending test. In addition, no changes were detected in circulating serum markers of bone turnover (P1NP, CTX-I, and osteocalcin). Gene expression monitoring also revealed no major impact of the loss of BRIL. Further, when mice were challenged with a surgically-induced fracture in tibia, bones repaired equally well in the KO mice as compared to WT. Finally, we showed that BRIL C-terminus is not a bona fide binding site for calcium. In conclusion, our in depth analysis suggest that skeletal patterning, bone mass accrual and remodeling in mice proceeded independent of BRIL. Public Library of Science 2017-09-07 /pmc/articles/PMC5589259/ /pubmed/28880886 http://dx.doi.org/10.1371/journal.pone.0184568 Text en © 2017 Patoine et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Patoine, Alexa
Husseini, Abdallah
Kasaai, Bahar
Gaumond, Marie-Hélène
Moffatt, Pierre
The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
title The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
title_full The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
title_fullStr The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
title_full_unstemmed The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
title_short The osteogenic cell surface marker BRIL/IFITM5 is dispensable for bone development and homeostasis in mice
title_sort osteogenic cell surface marker bril/ifitm5 is dispensable for bone development and homeostasis in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589259/
https://www.ncbi.nlm.nih.gov/pubmed/28880886
http://dx.doi.org/10.1371/journal.pone.0184568
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