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 - TY - JOUR A1 - Fromm, T. A1 - Jokat, W. A1 - Ryberg, T. A1 - Behrmann, Jan H. A1 - Haberland, C. A1 - Weber, Michael T1 - The onset of Walvis Ridge: Plume influence at the continental margin JF - Tectonophysics : international journal of geotectonics and the geology and physics of the interior of the earth N2 - The opening of the South Atlantic is a classical example for a plume related continental breakup. Flood basalts are present on both conjugate margins as well as aseismic ridges connecting them with the current plume location at Tristan da Cunha. To determine the effect of the proposed plume head on the continental crust, we acquired wide-angle seismic data at the junction of the Walvis Ridge with the African continent and modelled the P-wave velocity structure in a forward approach. The profile extends 430 km along the ridge and continues onshore to a length of 720 km. Crustal velocities beneath the Walvis Ridge vary between 5.5 km/s and 7.0 km/s, a typical range for oceanic crust. The crustal thickness of 22 km, however, is approximately three times larger than of normal oceanic crust. The continent-ocean transition is characterized by 30 km thick crust with strong lateral velocity variations in the upper crust and a high-velocity lower crust (HVLC), where velocities reach up to 7.5 km/s. The HVLC is 100 to 130 km wider at the Walvis Ridge than it is farther south, and impinges onto the continental crust of the Kaoko fold belt. Such high seismic velocities indicate Mg-rich igneous material intruded into the continental crust during the initial rifting stage. However, the remaining continental crust seems unaffected by intrusions and the root of the 40 km-thick crust of the Kaoko belt is not thermally abraded. We conclude that the plume head did not modify the continental crust on a large scale, but caused rather local effects. Thus, it seems unlikely that a plume drove or initiated the breakup process. We further propose that the plume already existed underneath the continent prior to the breakup, and ponded melt erupted at emerging rift structures providing the magma for continental flood basalts. (C) 2017 Elsevier B.V. All rights reserved. Y1 - 2017 U6 - https://doi.org/10.1016/j.tecto.2017.03.011 SN - 0040-1951 SN - 1879-3266 VL - 716 SP - 90 EP - 107 PB - Elsevier CY - Amsterdam ER -