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Collagen transport and related pathways in Osteogenesis Imperfecta
Osteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classific...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263409/ https://www.ncbi.nlm.nih.gov/pubmed/34169326 http://dx.doi.org/10.1007/s00439-021-02302-2 |
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author | Claeys, Lauria Storoni, Silvia Eekhoff, Marelise Elting, Mariet Wisse, Lisanne Pals, Gerard Bravenboer, Nathalie Maugeri, Alessandra Micha, Dimitra |
author_facet | Claeys, Lauria Storoni, Silvia Eekhoff, Marelise Elting, Mariet Wisse, Lisanne Pals, Gerard Bravenboer, Nathalie Maugeri, Alessandra Micha, Dimitra |
author_sort | Claeys, Lauria |
collection | PubMed |
description | Osteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classification and disease course prediction. Although collagen type I defects are long established as the primary cause of the bone pathology, we are still far from comprehending the complete mechanism. In the last years, the advent of next generation sequencing has triggered the discovery of many new genetic causes for OI, helping to draw its molecular landscape. It has become clear that, in addition to collagen type I genes, OI can be caused by multiple proteins connected to different parts of collagen biosynthesis. The production of collagen entails a complex process, starting from the production of the collagen Iα1 and collagen Iα2 chains in the endoplasmic reticulum, during and after which procollagen is subjected to a plethora of posttranslational modifications by chaperones. After reaching the Golgi organelle, procollagen is destined to the extracellular matrix where it forms collagen fibrils. Recently discovered mutations in components of the retrograde transport of chaperones highlight its emerging role as critical contributor of OI development. This review offers an overview of collagen regulation in the context of recent gene discoveries, emphasizing the significance of transport disruptions in the OI mechanism. We aim to motivate exploration of skeletal fragility in OI from the perspective of these pathways to identify regulatory points which can hint to therapeutic targets. |
format | Online Article Text |
id | pubmed-8263409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-82634092021-07-20 Collagen transport and related pathways in Osteogenesis Imperfecta Claeys, Lauria Storoni, Silvia Eekhoff, Marelise Elting, Mariet Wisse, Lisanne Pals, Gerard Bravenboer, Nathalie Maugeri, Alessandra Micha, Dimitra Hum Genet Review Osteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classification and disease course prediction. Although collagen type I defects are long established as the primary cause of the bone pathology, we are still far from comprehending the complete mechanism. In the last years, the advent of next generation sequencing has triggered the discovery of many new genetic causes for OI, helping to draw its molecular landscape. It has become clear that, in addition to collagen type I genes, OI can be caused by multiple proteins connected to different parts of collagen biosynthesis. The production of collagen entails a complex process, starting from the production of the collagen Iα1 and collagen Iα2 chains in the endoplasmic reticulum, during and after which procollagen is subjected to a plethora of posttranslational modifications by chaperones. After reaching the Golgi organelle, procollagen is destined to the extracellular matrix where it forms collagen fibrils. Recently discovered mutations in components of the retrograde transport of chaperones highlight its emerging role as critical contributor of OI development. This review offers an overview of collagen regulation in the context of recent gene discoveries, emphasizing the significance of transport disruptions in the OI mechanism. We aim to motivate exploration of skeletal fragility in OI from the perspective of these pathways to identify regulatory points which can hint to therapeutic targets. Springer Berlin Heidelberg 2021-06-24 2021 /pmc/articles/PMC8263409/ /pubmed/34169326 http://dx.doi.org/10.1007/s00439-021-02302-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Claeys, Lauria Storoni, Silvia Eekhoff, Marelise Elting, Mariet Wisse, Lisanne Pals, Gerard Bravenboer, Nathalie Maugeri, Alessandra Micha, Dimitra Collagen transport and related pathways in Osteogenesis Imperfecta |
title | Collagen transport and related pathways in Osteogenesis Imperfecta |
title_full | Collagen transport and related pathways in Osteogenesis Imperfecta |
title_fullStr | Collagen transport and related pathways in Osteogenesis Imperfecta |
title_full_unstemmed | Collagen transport and related pathways in Osteogenesis Imperfecta |
title_short | Collagen transport and related pathways in Osteogenesis Imperfecta |
title_sort | collagen transport and related pathways in osteogenesis imperfecta |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263409/ https://www.ncbi.nlm.nih.gov/pubmed/34169326 http://dx.doi.org/10.1007/s00439-021-02302-2 |
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