An Essential Physiological Role for MCT8 in Bone in Male Mice

Victoria D. Leitch, Caterina Di Cosmo, Xiao Hui Liao, Sam O'Boy, Thomas M. Galliford, Holly Evans, Peter I. Croucher, Alan Boyde, Alexandra Dumitrescu, Roy E Weiss, Samuel Refetoff, Graham R. Williams, J. H.Duncan Bassett

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3055-3066
Number of pages12
JournalEndocrinology
Volume158
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Knockout Mice
Thyroid Hormones
Bone and Bones
Bone Development
Chondrocytes
Maintenance
Physiologic Calcification
Growth Plate
X Chromosome
Osteogenesis
Osteoporosis
Hormones
Phenotype
Growth
Serum

ASJC Scopus subject areas

  • Endocrinology

Cite this

Leitch, V. D., Di Cosmo, C., Liao, X. H., O'Boy, S., Galliford, T. M., Evans, H., ... Bassett, J. H. D. (2017). An Essential Physiological Role for MCT8 in Bone in Male Mice. Endocrinology, 158(9), 3055-3066. https://doi.org/10.1210/en.2017-00399

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.

In: Endocrinology, Vol. 158, No. 9, 01.09.2017, p. 3055-3066.

Research output: Contribution to journalArticle

Leitch, VD, Di Cosmo, C, Liao, XH, O'Boy, S, Galliford, TM, Evans, H, Croucher, PI, Boyde, A, Dumitrescu, A, Weiss, RE, Refetoff, S, Williams, GR & Bassett, JHD 2017, 'An Essential Physiological Role for MCT8 in Bone in Male Mice', Endocrinology, vol. 158, no. 9, pp. 3055-3066. https://doi.org/10.1210/en.2017-00399
Leitch VD, Di Cosmo C, Liao XH, O'Boy S, Galliford TM, Evans H et al. An Essential Physiological Role for MCT8 in Bone in Male Mice. Endocrinology. 2017 Sep 1;158(9):3055-3066. https://doi.org/10.1210/en.2017-00399
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. In: Endocrinology. 2017 ; Vol. 158, No. 9. pp. 3055-3066.
@article{f04fd2f2dc9b4b04bee97fb86c03c5db,
title = "An Essential Physiological Role for MCT8 in Bone in Male Mice",
abstract = "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.",
author = "Leitch, {Victoria D.} and {Di Cosmo}, Caterina and Liao, {Xiao Hui} and Sam O'Boy and Galliford, {Thomas M.} and Holly Evans and Croucher, {Peter I.} and Alan Boyde and Alexandra Dumitrescu and Weiss, {Roy E} and Samuel Refetoff and Williams, {Graham R.} and Bassett, {J. H.Duncan}",
year = "2017",
month = "9",
day = "1",
doi = "10.1210/en.2017-00399",
language = "English (US)",
volume = "158",
pages = "3055--3066",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "9",

}

TY - JOUR

T1 - An Essential Physiological Role for MCT8 in Bone in Male Mice

AU - Leitch, Victoria D.

AU - Di Cosmo, Caterina

AU - Liao, Xiao Hui

AU - O'Boy, Sam

AU - Galliford, Thomas M.

AU - Evans, Holly

AU - Croucher, Peter I.

AU - Boyde, Alan

AU - Dumitrescu, Alexandra

AU - Weiss, Roy E

AU - Refetoff, Samuel

AU - Williams, Graham R.

AU - Bassett, J. H.Duncan

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85030614603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030614603&partnerID=8YFLogxK

U2 - 10.1210/en.2017-00399

DO - 10.1210/en.2017-00399

M3 - Article

C2 - 28637283

AN - SCOPUS:85030614603

VL - 158

SP - 3055

EP - 3066

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 9

ER -