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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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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. |
format | Online Article Text |
id | pubmed-7536578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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