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Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia

X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia, caused by inactivating mutations in the Phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. With aging, adult patients develop paradoxical heterotopic calcifications of tendons and ligaments at their insertion...

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Autores principales: Faraji-Bellée, Carole-Anne, Cauliez, Axelle, Salmon, Benjamin, Fogel, Olivier, Zhukouskaya, Volha, Benoit, Aurélie, Schinke, Thorsten, Roux, Christian, Linglart, Agnès, Miceli-Richard, Corinne, Chaussain, Catherine, Briot, Karine, Bardet, Claire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536578/
https://www.ncbi.nlm.nih.gov/pubmed/33072734
http://dx.doi.org/10.3389/fcell.2020.00854
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author Faraji-Bellée, Carole-Anne
Cauliez, Axelle
Salmon, Benjamin
Fogel, Olivier
Zhukouskaya, Volha
Benoit, Aurélie
Schinke, Thorsten
Roux, Christian
Linglart, Agnès
Miceli-Richard, Corinne
Chaussain, Catherine
Briot, Karine
Bardet, Claire
author_facet Faraji-Bellée, Carole-Anne
Cauliez, Axelle
Salmon, Benjamin
Fogel, Olivier
Zhukouskaya, Volha
Benoit, Aurélie
Schinke, Thorsten
Roux, Christian
Linglart, Agnès
Miceli-Richard, Corinne
Chaussain, Catherine
Briot, Karine
Bardet, Claire
author_sort Faraji-Bellée, Carole-Anne
collection PubMed
description X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia, caused by inactivating mutations in the Phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. With aging, adult patients develop paradoxical heterotopic calcifications of tendons and ligaments at their insertion sites (enthesophytes), and joint alterations. Understanding the progression of this structural damage that severely affects patients’ quality of life will help to improve the management of XLH. Here, we characterized the occurrence of enthesophytes and joint alterations through a 12 month in vivo micro-CT follow-up in the Hyp mouse, a murine model of XLH (n = 5 mice per group). Similar to adult patients with XLH, Hyp mice developed calcaneal enthesophytes, hip joint alterations, erosions of the sacroiliac joints and periarticular calcifications. These lesions were already present at month 3 and gradually worsened over time. In sharp contrast, no abnormalities were observed in control mice at early time points. Histological analyses confirmed the presence of bone erosions, calcifications and expansion of mineralizing enthesis fibrocartilage in Hyp mice and their absence in controls and suggested that new bone formation is driven by altered mechanical strain. Interestingly, despite a strong deformation of the curvature, none of the Hyp mice displayed enthesophyte at the spine. Peripheral enthesophytes and joint alterations develop at the early stages of the disease and gradually worsen overtime. Overall, our findings highlight the relevance of this preclinical model to test new therapies aiming to prevent bone and joint complications in XLH.
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spelling pubmed-75365782020-10-16 Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia Faraji-Bellée, Carole-Anne Cauliez, Axelle Salmon, Benjamin Fogel, Olivier Zhukouskaya, Volha Benoit, Aurélie Schinke, Thorsten Roux, Christian Linglart, Agnès Miceli-Richard, Corinne Chaussain, Catherine Briot, Karine Bardet, Claire Front Cell Dev Biol Cell and Developmental Biology X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia, caused by inactivating mutations in the Phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. With aging, adult patients develop paradoxical heterotopic calcifications of tendons and ligaments at their insertion sites (enthesophytes), and joint alterations. Understanding the progression of this structural damage that severely affects patients’ quality of life will help to improve the management of XLH. Here, we characterized the occurrence of enthesophytes and joint alterations through a 12 month in vivo micro-CT follow-up in the Hyp mouse, a murine model of XLH (n = 5 mice per group). Similar to adult patients with XLH, Hyp mice developed calcaneal enthesophytes, hip joint alterations, erosions of the sacroiliac joints and periarticular calcifications. These lesions were already present at month 3 and gradually worsened over time. In sharp contrast, no abnormalities were observed in control mice at early time points. Histological analyses confirmed the presence of bone erosions, calcifications and expansion of mineralizing enthesis fibrocartilage in Hyp mice and their absence in controls and suggested that new bone formation is driven by altered mechanical strain. Interestingly, despite a strong deformation of the curvature, none of the Hyp mice displayed enthesophyte at the spine. Peripheral enthesophytes and joint alterations develop at the early stages of the disease and gradually worsen overtime. Overall, our findings highlight the relevance of this preclinical model to test new therapies aiming to prevent bone and joint complications in XLH. Frontiers Media S.A. 2020-09-22 /pmc/articles/PMC7536578/ /pubmed/33072734 http://dx.doi.org/10.3389/fcell.2020.00854 Text en Copyright © 2020 Faraji-Bellée, Cauliez, Salmon, Fogel, Zhukouskaya, Benoit, Schinke, Roux, Linglart, Miceli-Richard, Chaussain, Briot and Bardet. http://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 Cell and Developmental Biology
Faraji-Bellée, Carole-Anne
Cauliez, Axelle
Salmon, Benjamin
Fogel, Olivier
Zhukouskaya, Volha
Benoit, Aurélie
Schinke, Thorsten
Roux, Christian
Linglart, Agnès
Miceli-Richard, Corinne
Chaussain, Catherine
Briot, Karine
Bardet, Claire
Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia
title Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia
title_full Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia
title_fullStr Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia
title_full_unstemmed Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia
title_short Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia
title_sort development of enthesopathies and joint structural damage in a murine model of x-linked hypophosphatemia
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536578/
https://www.ncbi.nlm.nih.gov/pubmed/33072734
http://dx.doi.org/10.3389/fcell.2020.00854
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