TY  - JOUR
A1  - Keller, Johannes
A1  - Catala-Lehnen, Philip
A1  - Huebner, Antje K.
A1  - Jeschke, Anke
A1  - Heckt, Timo
A1  - Lueth, Anja
A1  - Krause, Matthias
A1  - Koehne, Till
A1  - Albers, Joachim
A1  - Schulze, Jochen
A1  - Schilling, Sarah
A1  - Haberland, Michael
A1  - Denninger, Hannah
A1  - Neven, Mona
A1  - Hermans-Borgmeyer, Irm
A1  - Streichert, Thomas
A1  - Breer, Stefan
A1  - Barvencik, Florian
A1  - Levkau, Bodo
A1  - Rathkolb, Birgit
A1  - Wolf, Eckhard
A1  - Calzada-Wack, Julia
A1  - Neff, Frauke
A1  - Gailus-Durner, Valerie
A1  - Fuchs, Helmut
A1  - de Angelis, Martin Hrabe
A1  - Klutmann, Susanne
A1  - Tsourdi, Elena
A1  - Hofbauer, Lorenz C.
A1  - Kleuser, Burkhard
A1  - Chun, Jerold
A1  - Schinke, Thorsten
A1  - Amling, Michael
T1  - Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts
JF  - Nature Communications
N2  - 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 signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P(3). Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P(3)-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.
Y1  - 2014
U6  - https://doi.org/10.1038/ncomms6215
SN  - 2041-1723
VL  - 5
PB  - Nature Publ. Group
CY  - London
ER  -