Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts
| Autor: | Bodo Levkau, Till Koehne, Julia Calzada-Wack, Birgit Rathkolb, Jerold Chun, Thomas Streichert, Philip Catala-Lehnen, Joachim Albers, Hannah Denninger, Helmut Fuchs, Sarah Schilling, Anke Jeschke, Irm Hermans-Borgmeyer, Valerie Gailus-Durner, Elena Tsourdi, Florian Barvencik, Matthias Krause, Eckhard Wolf, Jochen Schulze, Stefan Breer, Martin Hrabĕ de Angelis, Johannes Keller, Susanne Klutmann, Frauke Neff, Michael Haberland, Michael Amling, Antje K. Huebner, Lorenz C. Hofbauer, Timo Heckt, Burkhard Kleuser, Mona Neven, Thorsten Schinke, Anja Lueth |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Calcitonin
Agonist medicine.medical_specialty medicine.drug_class Sphingosine-1-phosphate receptor Medizin Osteoclasts General Physics and Astronomy Mice Transgenic Biology Article Bone and Bones General Biochemistry Genetics and Molecular Biology Bone resorption Mice chemistry.chemical_compound Osteogenesis Sphingosine Osteoclast Internal medicine medicine Animals Collagenases Sphingosine-1-phosphate Receptor Alleles Crosses Genetic Osteoblasts Multidisciplinary General Chemistry Receptors Calcitonin Mice Inbred C57BL Phenotype Endocrinology medicine.anatomical_structure chemistry Osteoporosis Female lipids (amino acids peptides and proteins) Institut für Ernährungswissenschaft Lysophospholipids Porosity Signal Transduction |
| Zdroj: | Nat. Commun. 5:5215 (2014) Nature Communications |
| Popis: | 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. The regulatory role of calcitonin in bone homeostasis is well studied, yet its molecular activity is poorly understood. The authors show that calcitonin regulates bone cells function by inhibiting the osteoclast secretion of sphingosine 1-phosphate, a lipid mediator of osteoclast–osteoblast crosstalk. |
| Databáze: | OpenAIRE |
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