From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass 1
From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass 1
复制标题
DOI：
10.1177/153537020322800302
复制
发表时间：
2003-03
影响因子：
3.2
通讯作者：
S. Yakar;C. Rosen
中科院分区：
文献类型：
--
作者：
S. Yakar;C. Rosen
胰岛素样生长因子系统（IGF）通过大队列的流行病学分析和骨细胞的体外研究与骨获得过程有关。但是，骨中igf - 1表达与骨骼稳态或骨质疏松症等病理状况之间的确切关系仍不清楚。基因组工程的最新进展导致了更好的体内模型的发展，以测试igf - 1在成人骨骼发育和维持中的作用。现在已经确定igf - 1的骨骼表达对骨细胞分化功能至关重要。它也可能对甲状旁腺激素在小梁骨上的完全合成代谢作用和生物矿化的某些成分至关重要。来自条件诱变研究的证据表明，血清igf - 1在骨骼获得的最后阶段可能不仅仅是一个储存库或许可因子。这项工作根据这些较新的小鼠模型及其显着的骨骼表型，重新检查了“生长激素假说”的原始原则。该研究的意义深远，并提示操纵IGF调节系统的新方法可能有一天会成为治疗骨质疏松症的辅助疗法。
The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the “somatomedin hypothesis” in light of these newer mouse models and their remarkable skeletal phenotypes. The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis.