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The role of calcitonin and alpha-calcitonin gene-related peptide in bone formation |
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| Authors: | Huebner Antje K Keller Johannes Catala-Lehnen Philip Perkovic Sandra Streichert Thomas Emeson Ronald B Amling Michael Schinke Thorsten |
| Institution: | a Center of Biomechanics and Skeletal Biology, University Medical Center Hamburg—Eppendorf, Martinistrasse 52, Hamburg 20246, Germany b Department of Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg—Eppendorf, Hamburg 20246, Germany c Institute of Clinical Chemistry and Laboratory Diagnostics, Friedrich-Schiller-University, Jena 07740, Germany d Department of Clinical Chemistry, University Medical Center Hamburg—Eppendorf, Hamburg 20246, Germany e Departments of Pharmacology, Molecular Physiology, and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA |
| Abstract: | The Calca gene encodes two polypeptides, calcitonin (CT) and α-calcitonin gene-related peptide (α-CGRP), generated through alternative splicing. While CT, a hormone mainly produced by thyroidal C cells, has been described as a major regulator of bone resorption, α-CGRP, a neuropeptide expressed in the cells of the central and peripheral nervous system, is mostly known as a regulator of vascular tone. Surprisingly, the generation and skeletal analyses of two mouse deficiency models has recently uncovered a physiological function for both peptides in the regulation of bone formation. In the first model, where the replacement of exons 2-5 of the Calca gene resulted in the combined deficiency of CT and α-CGRP, an increased bone formation rate (BFR) was observed, whereas decreased BFR was found in the second model, where the introduction of a translational termination codon into exon 5 of the Calca gene resulted in the specific absence of α-CGRP. |
| Keywords: | Calcitonin CGRP Bone formation Osteoblast Bone resorption Osteoclast |
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