Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782264091493007360 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3607217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gualenibenedetta alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT devernejoulmariechristine alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT martymorieuxcaroline alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT deleonardisfabio alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT franchimarco alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT montiluca alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT forlinoantonella alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT houillierpascal alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT rossiantonio alterationofproteoglycansulfationaffectsbonegrowthandremodeling AT geoffroyvalerie alterationofproteoglycansulfationaffectsbonegrowthandremodeling |