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Keller, J.* ; Catala-Lehnen, P.* ; Huebner, A.K.* ; Jeschke, A.* ; Heckt, T.* ; Lueth, A.* ; Krause, M.* ; Koehne, T.* ; Albers, J.* ; Schulze, J.* ; Schilling, S.* ; Haberland, M.* ; Denninger, H.* ; Neven, M.* ; Hermans-Borgmeyer, I.* ; Streichert, T.* ; Breer, S.* ; Barvencik, F.* ; Levkau, B.* ; Rathkolb, B. ; Wolf, E.* ; Calzada-Wack, J. ; Neff, F. ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Klutmann, S.* ; Tsourdi, E.* ; Hofbauer, L.C.* ; Kleuser, B.* ; Chun, J.* ; Schinke, T.* ; Amling, M.*

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

Nat. Commun. 5:5215 (2014)
Verlagsversion DOI PMC
Open Access Gold
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gene-related Peptide; Protein-coupled Receptor; Mice Lacking; Multiple-sclerosis; Fingolimod Fty720; Endothelial-cells; Sphingosine-1-phosphate; Deletion; Mouse; Sepsis
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 5, Heft: , Seiten: , Artikelnummer: 5215 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)
POF Topic(s) 30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500600-001
G-500300-001
G-500600-003
G-501900-063
PubMed ID 25333900
DOI 10.1038/ncomms6215
WOS ID WOS:000343982800004
Erfassungsdatum 2014-10-22
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