Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts
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Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. / Keller, Johannes; Catala-Lehnen, Philip; Hübner, Antje K.; Jeschke, Anke; Heckt, Timo; Lueth, Anja; Krause, Matthias; Koehne, Till; Albers, Joachim; Schulze, Jochen; Schilling, Sarah; Haberland, M; Denninger, Hannah; Neven, Mona; Hermans-Borgmeyer, Irm; Streichert, Thomas; Breer, Stefan; Barvencik, Florian; Levkau, Bodo; Rathkolb, Birgit; Wolf, Eckhard; Calzada-Wack, Julia; Neff, Frauke; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabĕ; Klutmann, Susanne; Tsourdi, Elena; Hofbauer, Lorenz C; Kleuser, Burkhard; Chun, Jerold; Schinke, Thorsten; Amling, Michael.
in: NAT COMMUN, Jahrgang 5, 2014, S. 5215.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts
AU - Keller, Johannes
AU - Catala-Lehnen, Philip
AU - Hübner, Antje K.
AU - Jeschke, Anke
AU - Heckt, Timo
AU - Lueth, Anja
AU - Krause, Matthias
AU - Koehne, Till
AU - Albers, Joachim
AU - Schulze, Jochen
AU - Schilling, Sarah
AU - Haberland, M
AU - Denninger, Hannah
AU - Neven, Mona
AU - Hermans-Borgmeyer, Irm
AU - Streichert, Thomas
AU - Breer, Stefan
AU - Barvencik, Florian
AU - Levkau, Bodo
AU - Rathkolb, Birgit
AU - Wolf, Eckhard
AU - Calzada-Wack, Julia
AU - Neff, Frauke
AU - Gailus-Durner, Valerie
AU - Fuchs, Helmut
AU - de Angelis, Martin Hrabĕ
AU - Klutmann, Susanne
AU - Tsourdi, Elena
AU - Hofbauer, Lorenz C
AU - Kleuser, Burkhard
AU - Chun, Jerold
AU - Schinke, Thorsten
AU - Amling, Michael
PY - 2014
Y1 - 2014
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 S1P3. Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, 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.
AB - 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 S1P3. Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, 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.
U2 - 10.1038/ncomms6215
DO - 10.1038/ncomms6215
M3 - SCORING: Journal article
C2 - 25333900
VL - 5
SP - 5215
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
ER -