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Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo

Dacquin, R; Davey, RA; Laplace, C; Levasseur, G; Morris, HA; Goldring, SR; Gebre-Medhin, Samuel LU ; Galson, DL; Zajac, JD and Karsenty, G (2004) In Journal of Cell Biology 164(4). p.509-514
Abstract
Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic beta 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,... (More)
Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic beta 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mouse models, CALCR, islet amyloid polypeptide, CTR, osteoclast
in
Journal of Cell Biology
volume
164
issue
4
pages
509 - 514
publisher
Rockefeller University Press
external identifiers
  • wos:000189077200017
  • pmid:14970190
  • scopus:10744220002
ISSN
0021-9525
DOI
10.1083/jcb.200312135
language
English
LU publication?
yes
id
1b41b9c5-a4eb-4a98-8ae9-05373cd89337 (old id 287071)
date added to LUP
2007-08-02 12:02:07
date last changed
2017-08-27 03:58:46
@article{1b41b9c5-a4eb-4a98-8ae9-05373cd89337,
  abstract     = {Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic beta 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.},
  author       = {Dacquin, R and Davey, RA and Laplace, C and Levasseur, G and Morris, HA and Goldring, SR and Gebre-Medhin, Samuel and Galson, DL and Zajac, JD and Karsenty, G},
  issn         = {0021-9525},
  keyword      = {mouse models,CALCR,islet amyloid polypeptide,CTR,osteoclast},
  language     = {eng},
  number       = {4},
  pages        = {509--514},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo},
  url          = {http://dx.doi.org/10.1083/jcb.200312135},
  volume       = {164},
  year         = {2004},
}