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 i

ORGANISM(S): Mus musculus

SUBMITTER: Thomas Streichert 

PROVIDER: E-GEOD-60761 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress