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Endocrinology. 2017 Sep 1;158(9):3055-3066. doi: 10.1210/en.2017-00399.

An Essential Physiological Role for MCT8 in Bone in Male Mice.

Author information

1
Molecular Endocrinology Laboratory, Department of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, United Kingdom.
2
Department of Medicine, The University of Chicago, Chicago, Illinois 60637.
3
Sheffield Myeloma Research Team, University of Sheffield, Sheffield S10 2RX, United Kingdom.
4
The Garvan Institute of Medical Research and St. Vincent's Clinical School, University of New South Wales Medicine, Sydney, New South Wales 2010, Australia.
5
Queen Mary University of London, Oral Growth and Development, Bart's and The London School of Medicine and Dentistry, London E1 4NS, United Kingdom.
6
Department of Medicine, University of Miami, Miami, Florida 33136.
7
Department of Pediatrics, The University of Chicago, Chicago, Illinois 60637.
8
Committee on Genetics, The University of Chicago, Chicago, Illinois 60637.

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.

PMID:
28637283
PMCID:
PMC5659673
DOI:
10.1210/en.2017-00399
[Indexed for MEDLINE]
Free PMC Article

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