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Published 17 February 2004. doi:10.1083/jcb.200312135
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 4, 509-514
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Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo



Romain Dacquin1, Rachel A. Davey2, Catherine Laplace3, Régis Levasseur1, Howard A. Morris4, Steven R. Goldring3, Samuel Gebre-Medhin5, Deborah L. Galson3,6, Jeffrey D. Zajac2, and Gérard Karsenty1

1 Department of Molecular and Human Genetics and Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030
2 Department of Medicine, Austin Health, University of Melbourne, Victoria 3084 Australia
3 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115
4 Hanson Institute, Adelaide, South Australia 5000 Australia
5 Department of Clinical Genetics, Lund University Hospital, SE-221 85, Lund, Sweden
6 Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213

Address correspondence to Gerard Karsenty, Dept. of Molecular and Human Genetics and Bone Disease Program of Texas, Baylor College of Medicine, One Baylor Plaza, Room S921, Houston, TX 77030. Tel.: (713) 798-5489. Fax: (713) 798-1465. email: karsenty{at}bcm.tmc.edu

Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic ß cells. Cell culture assays suggest that amylin could affect bone formation and bone resorption, this latter function after its binding to the calcitonin receptor (CALCR). Here we show that Amylin inactivation leads to a low bone mass due to an increase in bone resorption, whereas bone formation is unaffected. In vitro, amylin inhibits fusion of mononucleated osteoclast precursors into multinucleated osteoclasts in an ERK1/2-dependent manner. Although Amylin +/- mice like Amylin-deficient mice display a low bone mass phenotype and increased bone resorption, Calcr +/- mice display a high bone mass due to an increase in bone formation. Moreover, compound heterozygote mice for Calcr and Amylin inactivation displayed bone abnormalities observed in both Calcr +/- and Amylin +/- mice, thereby ruling out that amylin uses CALCR to inhibit osteoclastogenesis in vivo. Thus, amylin is a physiological regulator of bone resorption that acts through an unidentified receptor.

Key Words: osteoclast; islet amyloid polypeptide; CTR; CALCR; mouse models

R. Dacquin and R.A. Davey contributed equally to this paper.

The online version of this article contains supplemental material.

Abbreviations used in this paper: BFR, bone formation rate; BMM, bone marrow macrophage; CALCR, calcitonin receptor; CGRP, calcitonin gene–related peptide; ERK1/2, extracellular signal–regulated protein kinase1/2; M-CSF, macrophage colony–stimulating factor; PTH, parathyroid hormone; RANKL, receptor activator of NF-{kappa}B ligand; TRAP, tartrate-resistant acid phosphatase; WT, wild-type.


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