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Alteration of proteoglycan sulfation affects bone growth and remodeling

Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype...

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Autores principales: Gualeni, Benedetta, de Vernejoul, Marie-Christine, Marty-Morieux, Caroline, De Leonardis, Fabio, Franchi, Marco, Monti, Luca, Forlino, Antonella, Houillier, Pascal, Rossi, Antonio, Geoffroy, Valerie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607217/
https://www.ncbi.nlm.nih.gov/pubmed/23369989
http://dx.doi.org/10.1016/j.bone.2013.01.036
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author Gualeni, Benedetta
de Vernejoul, Marie-Christine
Marty-Morieux, Caroline
De Leonardis, Fabio
Franchi, Marco
Monti, Luca
Forlino, Antonella
Houillier, Pascal
Rossi, Antonio
Geoffroy, Valerie
author_facet Gualeni, Benedetta
de Vernejoul, Marie-Christine
Marty-Morieux, Caroline
De Leonardis, Fabio
Franchi, Marco
Monti, Luca
Forlino, Antonella
Houillier, Pascal
Rossi, Antonio
Geoffroy, Valerie
author_sort Gualeni, Benedetta
collection PubMed
description Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis.
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spelling pubmed-36072172013-05-01 Alteration of proteoglycan sulfation affects bone growth and remodeling Gualeni, Benedetta de Vernejoul, Marie-Christine Marty-Morieux, Caroline De Leonardis, Fabio Franchi, Marco Monti, Luca Forlino, Antonella Houillier, Pascal Rossi, Antonio Geoffroy, Valerie Bone Original Full Length Article Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. Elsevier Science 2013-05 /pmc/articles/PMC3607217/ /pubmed/23369989 http://dx.doi.org/10.1016/j.bone.2013.01.036 Text en © 2013 Elsevier Inc. This document may be redistributed and reused, subject to certain conditions (http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0) .
spellingShingle Original Full Length Article
Gualeni, Benedetta
de Vernejoul, Marie-Christine
Marty-Morieux, Caroline
De Leonardis, Fabio
Franchi, Marco
Monti, Luca
Forlino, Antonella
Houillier, Pascal
Rossi, Antonio
Geoffroy, Valerie
Alteration of proteoglycan sulfation affects bone growth and remodeling
title Alteration of proteoglycan sulfation affects bone growth and remodeling
title_full Alteration of proteoglycan sulfation affects bone growth and remodeling
title_fullStr Alteration of proteoglycan sulfation affects bone growth and remodeling
title_full_unstemmed Alteration of proteoglycan sulfation affects bone growth and remodeling
title_short Alteration of proteoglycan sulfation affects bone growth and remodeling
title_sort alteration of proteoglycan sulfation affects bone growth and remodeling
topic Original Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607217/
https://www.ncbi.nlm.nih.gov/pubmed/23369989
http://dx.doi.org/10.1016/j.bone.2013.01.036
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