Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias

Transient Receptor Potential Vanilloid 4 (TRPV4) is a mechano- and osmosensitive cation channel that is highly expressed in chondrocytes, the cells in cartilage. A large number of mutations in TRPV4 have been linked to skeletal dysplasias, and the goal of this addendum is to shed light on the mechan...

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Autores principales: Leddy, Holly A, McNulty, Amy L, Guilak, Farshid, Liedtke, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755236/
https://www.ncbi.nlm.nih.gov/pubmed/26942100
http://dx.doi.org/10.4161/2167549X.2014.962971
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author Leddy, Holly A
McNulty, Amy L
Guilak, Farshid
Liedtke, Wolfgang
author_facet Leddy, Holly A
McNulty, Amy L
Guilak, Farshid
Liedtke, Wolfgang
author_sort Leddy, Holly A
collection PubMed
description Transient Receptor Potential Vanilloid 4 (TRPV4) is a mechano- and osmosensitive cation channel that is highly expressed in chondrocytes, the cells in cartilage. A large number of mutations in TRPV4 have been linked to skeletal dysplasias, and the goal of this addendum is to shed light on the mechanisms by which mutations in TRPV4 can cause skeletal dysplasias by focusing on 3 recent publications. These papers suggest that skeletal dysplasia-causing TRPV4 mutations reprogram chondrocytes to increase follistatin production, which inhibits BMP signaling, thus slowing the process of endochondral ossification and leading to skeletal dysplasia. In spite of these important advances in our understanding of the disease mechanism, much remains to be elucidated. Nonetheless, these new data suggest that inhibiting aberrant TRPV4 activity in the cartilage may be a promising direction for therapeutic intervention.
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spelling pubmed-47552362016-03-03 Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias Leddy, Holly A McNulty, Amy L Guilak, Farshid Liedtke, Wolfgang Rare Dis Addendum Transient Receptor Potential Vanilloid 4 (TRPV4) is a mechano- and osmosensitive cation channel that is highly expressed in chondrocytes, the cells in cartilage. A large number of mutations in TRPV4 have been linked to skeletal dysplasias, and the goal of this addendum is to shed light on the mechanisms by which mutations in TRPV4 can cause skeletal dysplasias by focusing on 3 recent publications. These papers suggest that skeletal dysplasia-causing TRPV4 mutations reprogram chondrocytes to increase follistatin production, which inhibits BMP signaling, thus slowing the process of endochondral ossification and leading to skeletal dysplasia. In spite of these important advances in our understanding of the disease mechanism, much remains to be elucidated. Nonetheless, these new data suggest that inhibiting aberrant TRPV4 activity in the cartilage may be a promising direction for therapeutic intervention. Taylor & Francis 2014-10-30 /pmc/articles/PMC4755236/ /pubmed/26942100 http://dx.doi.org/10.4161/2167549X.2014.962971 Text en © 2014 The Author(s). © 2014 Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Addendum
Leddy, Holly A
McNulty, Amy L
Guilak, Farshid
Liedtke, Wolfgang
Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias
title Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias
title_full Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias
title_fullStr Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias
title_full_unstemmed Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias
title_short Unraveling the mechanism by which TRPV4 mutations cause skeletal dysplasias
title_sort unraveling the mechanism by which trpv4 mutations cause skeletal dysplasias
topic Addendum
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755236/
https://www.ncbi.nlm.nih.gov/pubmed/26942100
http://dx.doi.org/10.4161/2167549X.2014.962971
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