ArrayExpress Uploader0mouseuntreatedwildtypeuntreatedwildtypeuntreatedwildtypeCalcitoninwildtypeCalcitoninwildtypeCalcitoninwildtypeuntreatedCalcr-/-untreatedCalcr-/-untreatedCalcr-/-CalcitoninCalcr-/-CalcitoninCalcr-/-CalcitoninCalcr-/-7695arrayexpress_sid6The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice...E-GEOD-60761/profile/8773/arrayexpressuploader212bonecalcitoninhormonelipidosteoclastDec.12, 2014Falsecalcitonin-controls-bone-formation-by-inhibiting-tE-GEOD-60761_A-AFFY-45Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclastsNov.12, 2014The 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.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-60761http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-60761/samples/