The role of calcitonin and alpha-calcitonin gene-related peptide in bone formation.
The Calca gene encodes two polypeptides, calcitonin (CT) and alpha-calcitonin gene-related peptide (alpha-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, alpha-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 alpha-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 alpha-CGRP.
Huebner
Antje K
AK
Center of Biomechanics and Skeletal Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Keller
Johannes
J
Catala-Lehnen
Philip
P
Perkovic
Sandra
S
Streichert
Thomas
T
Emeson
Ronald B
RB
Amling
Michael
M
Schinke
Thorsten
T
D017398:Alternative Splicing; D000818:Animals; D002116:Calcitonin / Q000235:genetics / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010012:Osteogenesis / Q000502:physiology*
D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide