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Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome

Loss-of-function mutations in carbohydrate sulfotransferase 14 (CHST14) cause musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovasc...

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Autores principales: Hashimoto, Ayana, Hirose, Takuya, Hashimoto, Kohei, Mizumoto, Shuji, Nitahara-Kasahara, Yuko, Saka, Shota, Yoshizawa, Takahiro, Okada, Takashi, Yamada, Shuhei, Kosho, Tomoki, Watanabe, Takafumi, Miyata, Shinji, Nomura, Yoshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957042/
https://www.ncbi.nlm.nih.gov/pubmed/36833235
http://dx.doi.org/10.3390/genes14020308
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author Hashimoto, Ayana
Hirose, Takuya
Hashimoto, Kohei
Mizumoto, Shuji
Nitahara-Kasahara, Yuko
Saka, Shota
Yoshizawa, Takahiro
Okada, Takashi
Yamada, Shuhei
Kosho, Tomoki
Watanabe, Takafumi
Miyata, Shinji
Nomura, Yoshihiro
author_facet Hashimoto, Ayana
Hirose, Takuya
Hashimoto, Kohei
Mizumoto, Shuji
Nitahara-Kasahara, Yuko
Saka, Shota
Yoshizawa, Takahiro
Okada, Takashi
Yamada, Shuhei
Kosho, Tomoki
Watanabe, Takafumi
Miyata, Shinji
Nomura, Yoshihiro
author_sort Hashimoto, Ayana
collection PubMed
description Loss-of-function mutations in carbohydrate sulfotransferase 14 (CHST14) cause musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral and ocular system. The replacement of dermatan sulfate chains on decorin proteoglycan with chondroitin sulfate chains is proposed to lead to the disorganization of collagen networks in the skin. However, the pathogenic mechanisms of mcEDS-CHST14 are not fully understood, partly due to the lack of in vitro models of this disease. In the present study, we established in vitro models of fibroblast-mediated collagen network formation that recapacitate mcEDS-CHST14 pathology. Electron microscopy analysis of mcEDS-CHST14-mimicking collagen gels revealed an impaired fibrillar organization that resulted in weaker mechanical strength of the gels. The addition of decorin isolated from patients with mcEDS-CHST14 and Chst14(−/−) mice disturbed the assembly of collagen fibrils in vitro compared to control decorin. Our study may provide useful in vitro models of mcEDS-CHST14 to elucidate the pathomechanism of this disease.
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spelling pubmed-99570422023-02-25 Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome Hashimoto, Ayana Hirose, Takuya Hashimoto, Kohei Mizumoto, Shuji Nitahara-Kasahara, Yuko Saka, Shota Yoshizawa, Takahiro Okada, Takashi Yamada, Shuhei Kosho, Tomoki Watanabe, Takafumi Miyata, Shinji Nomura, Yoshihiro Genes (Basel) Article Loss-of-function mutations in carbohydrate sulfotransferase 14 (CHST14) cause musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral and ocular system. The replacement of dermatan sulfate chains on decorin proteoglycan with chondroitin sulfate chains is proposed to lead to the disorganization of collagen networks in the skin. However, the pathogenic mechanisms of mcEDS-CHST14 are not fully understood, partly due to the lack of in vitro models of this disease. In the present study, we established in vitro models of fibroblast-mediated collagen network formation that recapacitate mcEDS-CHST14 pathology. Electron microscopy analysis of mcEDS-CHST14-mimicking collagen gels revealed an impaired fibrillar organization that resulted in weaker mechanical strength of the gels. The addition of decorin isolated from patients with mcEDS-CHST14 and Chst14(−/−) mice disturbed the assembly of collagen fibrils in vitro compared to control decorin. Our study may provide useful in vitro models of mcEDS-CHST14 to elucidate the pathomechanism of this disease. MDPI 2023-01-24 /pmc/articles/PMC9957042/ /pubmed/36833235 http://dx.doi.org/10.3390/genes14020308 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hashimoto, Ayana
Hirose, Takuya
Hashimoto, Kohei
Mizumoto, Shuji
Nitahara-Kasahara, Yuko
Saka, Shota
Yoshizawa, Takahiro
Okada, Takashi
Yamada, Shuhei
Kosho, Tomoki
Watanabe, Takafumi
Miyata, Shinji
Nomura, Yoshihiro
Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
title Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
title_full Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
title_fullStr Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
title_full_unstemmed Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
title_short Collagen Network Formation in In Vitro Models of Musculocontractural Ehlers–Danlos Syndrome
title_sort collagen network formation in in vitro models of musculocontractural ehlers–danlos syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957042/
https://www.ncbi.nlm.nih.gov/pubmed/36833235
http://dx.doi.org/10.3390/genes14020308
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