Dataset Information


Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts

ABSTRACT: The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signaling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P3. Finally, pharmacologic treatment with the non-selective S1P receptor agonist FTY720 causes increased bone formation in wildtype, but not in S1P3-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo, and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts. Osteoclasts of wildtype and Calcr-/- C57Bl/6 mice were treated with Calcitonin and compared to the non-treated osteoclasts of wildtype or Calcr-/- mice, respectively.

ORGANISM(S): Mus musculus  

SUBMITTER: Thorsten Schinke   Thomas Streichert 

PROVIDER: E-GEOD-60761 | ArrayExpress | 2014-10-19



Similar Datasets

2012-08-18 | E-GEOD-37219 | ArrayExpress
2010-03-22 | E-GEOD-20850 | ArrayExpress
2015-04-01 | E-GEOD-45656 | ArrayExpress
2015-12-31 | E-GEOD-53017 | ArrayExpress
2015-02-23 | E-GEOD-59387 | ArrayExpress
2011-09-30 | E-GEOD-29107 | ArrayExpress
2013-08-30 | E-GEOD-46648 | ArrayExpress
2011-09-30 | E-GEOD-29106 | ArrayExpress
2014-06-02 | E-GEOD-58146 | ArrayExpress
2015-12-18 | E-MTAB-4155 | ArrayExpress