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HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas
Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256178/ https://www.ncbi.nlm.nih.gov/pubmed/22253766 http://dx.doi.org/10.1371/journal.pone.0029734 |
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author | Wiweger, Malgorzata I. Zhao, Zhe van Merkesteyn, Richard J. P. Roehl, Henry H. Hogendoorn, Pancras C. W. |
author_facet | Wiweger, Malgorzata I. Zhao, Zhe van Merkesteyn, Richard J. P. Roehl, Henry H. Hogendoorn, Pancras C. W. |
author_sort | Wiweger, Malgorzata I. |
collection | PubMed |
description | Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2) are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2(−/−) fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2(−/−) fish. Histological analysis reveals that ext2(−/−) fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2(−/−) fish have a single tooth at the end of the 5(th) pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2(−/−) teeth have abnormal morphology (they were shorter and thicker than in the WT) and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2(+/−) adults. The tooth morphology in ext2(−/−) was partially rescued by FGF8 administered locally (bead implants). Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems. |
format | Online Article Text |
id | pubmed-3256178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32561782012-01-17 HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas Wiweger, Malgorzata I. Zhao, Zhe van Merkesteyn, Richard J. P. Roehl, Henry H. Hogendoorn, Pancras C. W. PLoS One Research Article Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2) are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2(−/−) fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2(−/−) fish. Histological analysis reveals that ext2(−/−) fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2(−/−) fish have a single tooth at the end of the 5(th) pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2(−/−) teeth have abnormal morphology (they were shorter and thicker than in the WT) and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2(+/−) adults. The tooth morphology in ext2(−/−) was partially rescued by FGF8 administered locally (bead implants). Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems. Public Library of Science 2012-01-11 /pmc/articles/PMC3256178/ /pubmed/22253766 http://dx.doi.org/10.1371/journal.pone.0029734 Text en Wiweger et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wiweger, Malgorzata I. Zhao, Zhe van Merkesteyn, Richard J. P. Roehl, Henry H. Hogendoorn, Pancras C. W. HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas |
title | HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas |
title_full | HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas |
title_fullStr | HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas |
title_full_unstemmed | HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas |
title_short | HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas |
title_sort | hspg-deficient zebrafish uncovers dental aspect of multiple osteochondromas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256178/ https://www.ncbi.nlm.nih.gov/pubmed/22253766 http://dx.doi.org/10.1371/journal.pone.0029734 |
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