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An Essential Physiological Role for MCT8 in Bone in Male Mice

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transpor...

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Autores principales: Leitch, Victoria D., Di Cosmo, Caterina, Liao, Xiao-Hui, O’Boy, Sam, Galliford, Thomas M., Evans, Holly, Croucher, Peter I., Boyde, Alan, Dumitrescu, Alexandra, Weiss, Roy E., Refetoff, Samuel, Williams, Graham R., Bassett, J. H. Duncan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659673/
https://www.ncbi.nlm.nih.gov/pubmed/28637283
http://dx.doi.org/10.1210/en.2017-00399
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author Leitch, Victoria D.
Di Cosmo, Caterina
Liao, Xiao-Hui
O’Boy, Sam
Galliford, Thomas M.
Evans, Holly
Croucher, Peter I.
Boyde, Alan
Dumitrescu, Alexandra
Weiss, Roy E.
Refetoff, Samuel
Williams, Graham R.
Bassett, J. H. Duncan
author_facet Leitch, Victoria D.
Di Cosmo, Caterina
Liao, Xiao-Hui
O’Boy, Sam
Galliford, Thomas M.
Evans, Holly
Croucher, Peter I.
Boyde, Alan
Dumitrescu, Alexandra
Weiss, Roy E.
Refetoff, Samuel
Williams, Graham R.
Bassett, J. H. Duncan
author_sort Leitch, Victoria D.
collection PubMed
description T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance.
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spelling pubmed-56596732017-11-27 An Essential Physiological Role for MCT8 in Bone in Male Mice Leitch, Victoria D. Di Cosmo, Caterina Liao, Xiao-Hui O’Boy, Sam Galliford, Thomas M. Evans, Holly Croucher, Peter I. Boyde, Alan Dumitrescu, Alexandra Weiss, Roy E. Refetoff, Samuel Williams, Graham R. Bassett, J. H. Duncan Endocrinology Research Articles T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance. Endocrine Society 2017-06-15 /pmc/articles/PMC5659673/ /pubmed/28637283 http://dx.doi.org/10.1210/en.2017-00399 Text en https://creativecommons.org/licenses/by/4.0/ This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
spellingShingle Research Articles
Leitch, Victoria D.
Di Cosmo, Caterina
Liao, Xiao-Hui
O’Boy, Sam
Galliford, Thomas M.
Evans, Holly
Croucher, Peter I.
Boyde, Alan
Dumitrescu, Alexandra
Weiss, Roy E.
Refetoff, Samuel
Williams, Graham R.
Bassett, J. H. Duncan
An Essential Physiological Role for MCT8 in Bone in Male Mice
title An Essential Physiological Role for MCT8 in Bone in Male Mice
title_full An Essential Physiological Role for MCT8 in Bone in Male Mice
title_fullStr An Essential Physiological Role for MCT8 in Bone in Male Mice
title_full_unstemmed An Essential Physiological Role for MCT8 in Bone in Male Mice
title_short An Essential Physiological Role for MCT8 in Bone in Male Mice
title_sort essential physiological role for mct8 in bone in male mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659673/
https://www.ncbi.nlm.nih.gov/pubmed/28637283
http://dx.doi.org/10.1210/en.2017-00399
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