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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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00854/full |
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| author | Carole-Anne Faraji-Bellée Axelle Cauliez Benjamin Salmon Benjamin Salmon Olivier Fogel Volha Zhukouskaya Volha Zhukouskaya Aurélie Benoit Thorsten Schinke Christian Roux Agnès Linglart Agnès Linglart Agnès Linglart Corinne Miceli-Richard Catherine Chaussain Catherine Chaussain Catherine Chaussain Karine Briot Karine Briot Claire Bardet |
| author_facet | Carole-Anne Faraji-Bellée Axelle Cauliez Benjamin Salmon Benjamin Salmon Olivier Fogel Volha Zhukouskaya Volha Zhukouskaya Aurélie Benoit Thorsten Schinke Christian Roux Agnès Linglart Agnès Linglart Agnès Linglart Corinne Miceli-Richard Catherine Chaussain Catherine Chaussain Catherine Chaussain Karine Briot Karine Briot Claire Bardet |
| author_sort | Carole-Anne Faraji-Bellée |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T00:21:33Z |
| format | Article |
| id | doaj.art-9c9b4e95b4994f3ba7f2144dbb94b22e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T00:21:33Z |
| publishDate | 2020-09-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-9c9b4e95b4994f3ba7f2144dbb94b22e2022-12-21T23:25:12ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-09-01810.3389/fcell.2020.00854569839Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked HypophosphatemiaCarole-Anne Faraji-Bellée0Axelle Cauliez1Benjamin Salmon2Benjamin Salmon3Olivier Fogel4Volha Zhukouskaya5Volha Zhukouskaya6Aurélie Benoit7Thorsten Schinke8Christian Roux9Agnès Linglart10Agnès Linglart11Agnès Linglart12Corinne Miceli-Richard13Catherine Chaussain14Catherine Chaussain15Catherine Chaussain16Karine Briot17Karine Briot18Claire Bardet19Université de Paris, Laboratory Orofacial Pathologies, Imaging and Biotherapies UR 2496, Dental School, Montrouge, FranceUniversité de Paris, Laboratory Orofacial Pathologies, Imaging and Biotherapies UR 2496, Dental School, Montrouge, FranceUniversité de Paris, Laboratory Orofacial Pathologies, Imaging and Biotherapies UR 2496, Dental School, Montrouge, FranceAPHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Dental Medicine Department, Bretonneau Hospital, Paris, FranceDepartment of Rheumatology, Cochin Hospital, Université de Paris, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, and Reference Center for Rare Genetic Bone Diseases, Cochin Hospital, Paris, FranceUniversité de Paris, Laboratory Orofacial Pathologies, Imaging and Biotherapies UR 2496, Dental School, Montrouge, FranceAPHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, FranceUniversité de Paris, URB2I, UR 4462, Dental School, Montrouge, FranceDepartment of Osteology and Biomechanics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Rheumatology, Cochin Hospital, Université de Paris, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, and Reference Center for Rare Genetic Bone Diseases, Cochin Hospital, Paris, FranceAPHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, FranceAPHP, Department of Endocrinology and Diabetology for Children, Bicêtre Paris Sud Hospital, Le Kremlin-Bicêtre, FranceParis Sud – Paris Saclay University, Faculté de Médecine, Le Kremlin – Bicêtre, FranceDepartment of Rheumatology, Cochin Hospital, Université de Paris, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, and Reference Center for Rare Genetic Bone Diseases, Cochin Hospital, Paris, FranceUniversité de Paris, Laboratory Orofacial Pathologies, Imaging and Biotherapies UR 2496, Dental School, Montrouge, FranceAPHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Dental Medicine Department, Bretonneau Hospital, Paris, FranceAPHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, FranceDepartment of Rheumatology, Cochin Hospital, Université de Paris, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, and Reference Center for Rare Genetic Bone Diseases, Cochin Hospital, Paris, FranceAPHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Sud Hospital, Le Kremlin Bicêtre, FranceUniversité de Paris, Laboratory Orofacial Pathologies, Imaging and Biotherapies UR 2496, Dental School, Montrouge, FranceX-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.https://www.frontiersin.org/article/10.3389/fcell.2020.00854/fullHyp mousenatural historyenthesophytejoint alterationXLH |
| spellingShingle | Carole-Anne Faraji-Bellée Axelle Cauliez Benjamin Salmon Benjamin Salmon Olivier Fogel Volha Zhukouskaya Volha Zhukouskaya Aurélie Benoit Thorsten Schinke Christian Roux Agnès Linglart Agnès Linglart Agnès Linglart Corinne Miceli-Richard Catherine Chaussain Catherine Chaussain Catherine Chaussain Karine Briot Karine Briot Claire Bardet Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia Frontiers in Cell and Developmental Biology Hyp mouse natural history enthesophyte joint alteration XLH |
| 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 | Hyp mouse natural history enthesophyte joint alteration XLH |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00854/full |
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