Huebner Antje K, Keller Johannes, Catala-Lehnen Philip, Perkovic Sandra, Streichert Thomas, Emeson Ronald B, Amling Michael, Schinke Thorsten
Center of Biomechanics and Skeletal Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Arch Biochem Biophys. 2008 May 15;473(2):210-7. doi: 10.1016/j.abb.2008.02.013. Epub 2008 Feb 16.
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.
Calca基因通过可变剪接编码两种多肽，即降钙素（CT）和α-降钙素基因相关肽（α-CGRP）。虽然CT主要由甲状腺C细胞产生，是一种已被描述为骨吸收主要调节因子的激素，但α-CGRP是一种在中枢和外周神经系统细胞中表达的神经肽，主要作为血管张力的调节因子为人所知。令人惊讶的是，最近对两种小鼠缺陷模型的生成和骨骼分析揭示了这两种肽在调节骨形成中的生理功能。在第一个模型中，Calca基因外显子2-5的替换导致CT和α-CGRP联合缺乏，观察到骨形成率（BFR）增加，而在第二个模型中发现BFR降低，在该模型中，在Calca基因外显子5中引入翻译终止密码子导致α-CGRP特异性缺失。
