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Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene

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Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. / Hoff, Ana O; Catala-Lehnen, Philip; Thomas, Pamela M; Priemel, Matthias; Rueger, Johannes M; Nasonkin, Igor; Bradley, Allan; Hughes, Mark R; Ordonez, Nelson; Cote, Gilbert J; Amling, Michael; Gagel, Robert F.

In: J CLIN INVEST, Vol. 110, No. 12, 12.2002, p. 1849-57.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hoff, AO, Catala-Lehnen, P, Thomas, PM, Priemel, M, Rueger, JM, Nasonkin, I, Bradley, A, Hughes, MR, Ordonez, N, Cote, GJ, Amling, M & Gagel, RF 2002, 'Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene', J CLIN INVEST, vol. 110, no. 12, pp. 1849-57. https://doi.org/10.1172/JCI14218

APA

Hoff, A. O., Catala-Lehnen, P., Thomas, P. M., Priemel, M., Rueger, J. M., Nasonkin, I., Bradley, A., Hughes, M. R., Ordonez, N., Cote, G. J., Amling, M., & Gagel, R. F. (2002). Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. J CLIN INVEST, 110(12), 1849-57. https://doi.org/10.1172/JCI14218

Vancouver

Hoff AO, Catala-Lehnen P, Thomas PM, Priemel M, Rueger JM, Nasonkin I et al. Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. J CLIN INVEST. 2002 Dec;110(12):1849-57. https://doi.org/10.1172/JCI14218

Bibtex

@article{4bdbbd93caa24c119d094f7f3972e3c6,
title = "Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene",
abstract = "Calcitonin (CT) is a known inhibitor of bone resorption. Calcitonin gene-related peptide-alpha (CGRPalpha), produced by alternative RNA processing of the CT/CGRP gene, has no clearly defined role in bone. To better understand the physiologic role of the CT/CGRP gene we created a mouse in which the coding sequences for both CT and CGRPalpha were deleted by homologous recombination. The CT/CGRP(-/-) knockout (KO) mice procreated normally, there were no identifiable developmental defects at birth, and they had normal baseline calcium-related chemistry values. However, KO animals were more responsive to exogenous human parathyroid hormone as evidenced by a greater increase of the serum calcium concentration and urine deoxypyridinoline crosslinks, an effect reversed by CT and mediated by a greater increase in bone resorption than in controls. Surprisingly, KO mice have significantly greater trabecular bone volume and a 1.5- to 2-fold increase in bone formation at 1 and 3 months of age. This effect appears to be mediated by increased bone formation. In addition, KO mice maintain bone mass following ovariectomy, whereas wild-type mice lose approximately one-third of their bone mass over 2 months. These findings argue for dual roles for CT/CGRP gene products: prevention of bone resorption in hypercalcemic states and a regulatory role in bone formation.",
keywords = "Alternative Splicing, Animals, Bone Density, Bone Resorption, Bone and Bones/anatomy & histology, Calcitonin/genetics, Calcitonin Gene-Related Peptide/genetics, Estrogens/deficiency, Female, Gene Deletion, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Osteoclasts/metabolism, Osteogenesis, Ovariectomy, Parathyroid Hormone/metabolism, Phenotype, Radiography, Thyroid Gland/cytology",
author = "Hoff, {Ana O} and Philip Catala-Lehnen and Thomas, {Pamela M} and Matthias Priemel and Rueger, {Johannes M} and Igor Nasonkin and Allan Bradley and Hughes, {Mark R} and Nelson Ordonez and Cote, {Gilbert J} and Michael Amling and Gagel, {Robert F}",
year = "2002",
month = dec,
doi = "10.1172/JCI14218",
language = "English",
volume = "110",
pages = "1849--57",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

RIS

TY - JOUR

T1 - Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene

AU - Hoff, Ana O

AU - Catala-Lehnen, Philip

AU - Thomas, Pamela M

AU - Priemel, Matthias

AU - Rueger, Johannes M

AU - Nasonkin, Igor

AU - Bradley, Allan

AU - Hughes, Mark R

AU - Ordonez, Nelson

AU - Cote, Gilbert J

AU - Amling, Michael

AU - Gagel, Robert F

PY - 2002/12

Y1 - 2002/12

N2 - Calcitonin (CT) is a known inhibitor of bone resorption. Calcitonin gene-related peptide-alpha (CGRPalpha), produced by alternative RNA processing of the CT/CGRP gene, has no clearly defined role in bone. To better understand the physiologic role of the CT/CGRP gene we created a mouse in which the coding sequences for both CT and CGRPalpha were deleted by homologous recombination. The CT/CGRP(-/-) knockout (KO) mice procreated normally, there were no identifiable developmental defects at birth, and they had normal baseline calcium-related chemistry values. However, KO animals were more responsive to exogenous human parathyroid hormone as evidenced by a greater increase of the serum calcium concentration and urine deoxypyridinoline crosslinks, an effect reversed by CT and mediated by a greater increase in bone resorption than in controls. Surprisingly, KO mice have significantly greater trabecular bone volume and a 1.5- to 2-fold increase in bone formation at 1 and 3 months of age. This effect appears to be mediated by increased bone formation. In addition, KO mice maintain bone mass following ovariectomy, whereas wild-type mice lose approximately one-third of their bone mass over 2 months. These findings argue for dual roles for CT/CGRP gene products: prevention of bone resorption in hypercalcemic states and a regulatory role in bone formation.

AB - Calcitonin (CT) is a known inhibitor of bone resorption. Calcitonin gene-related peptide-alpha (CGRPalpha), produced by alternative RNA processing of the CT/CGRP gene, has no clearly defined role in bone. To better understand the physiologic role of the CT/CGRP gene we created a mouse in which the coding sequences for both CT and CGRPalpha were deleted by homologous recombination. The CT/CGRP(-/-) knockout (KO) mice procreated normally, there were no identifiable developmental defects at birth, and they had normal baseline calcium-related chemistry values. However, KO animals were more responsive to exogenous human parathyroid hormone as evidenced by a greater increase of the serum calcium concentration and urine deoxypyridinoline crosslinks, an effect reversed by CT and mediated by a greater increase in bone resorption than in controls. Surprisingly, KO mice have significantly greater trabecular bone volume and a 1.5- to 2-fold increase in bone formation at 1 and 3 months of age. This effect appears to be mediated by increased bone formation. In addition, KO mice maintain bone mass following ovariectomy, whereas wild-type mice lose approximately one-third of their bone mass over 2 months. These findings argue for dual roles for CT/CGRP gene products: prevention of bone resorption in hypercalcemic states and a regulatory role in bone formation.

KW - Alternative Splicing

KW - Animals

KW - Bone Density

KW - Bone Resorption

KW - Bone and Bones/anatomy & histology

KW - Calcitonin/genetics

KW - Calcitonin Gene-Related Peptide/genetics

KW - Estrogens/deficiency

KW - Female

KW - Gene Deletion

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Osteoclasts/metabolism

KW - Osteogenesis

KW - Ovariectomy

KW - Parathyroid Hormone/metabolism

KW - Phenotype

KW - Radiography

KW - Thyroid Gland/cytology

U2 - 10.1172/JCI14218

DO - 10.1172/JCI14218

M3 - SCORING: Journal article

C2 - 12488435

VL - 110

SP - 1849

EP - 1857

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 12

ER -