Kubota Takuo, Elalieh Hashem Z, Saless Neema, Fong Chak, Wang Yongmei, Babey Muriel, Cheng Zhiqiang, Bikle Daniel D
Department of Medicine, University of California San Francisco and Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, 4150 Clement St, 111N, San Francisco, CA 94121, USA.
Acta Astronaut. 2013 Nov;92(1):73-78. doi: 10.1016/j.actaastro.2012.08.007.
Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor 1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific deficient ( ) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.
骨骼的加载和卸载对骨重塑有显著影响，这一过程也受胰岛素样生长因子1（IGF-1）信号通路调控。骨骼卸载会导致对IGF-1合成代谢作用产生抵抗，而卸载后重新加载则可恢复对IGF-1的反应性。然而，关于IGF-1信号通路在骨骼对机械负荷反应中的重要性的直接研究仍有待验证。在本研究中，我们评估了成骨细胞特异性缺陷（ ）小鼠对卸载和重新加载的骨骼反应。将小鼠后肢卸载14天，然后重新加载16天。 小鼠在基线时皮质骨较小，骨膜和骨内膜骨形成减少。在 小鼠中，骨膜和骨内膜骨形成随卸载而减少。然而，尽管重新加载诱导的骨内膜骨形成未受阻碍，但在 小鼠中，重新加载时骨膜骨形成的恢复被完全抑制。与对照小鼠相比，这些骨形成的变化导致 小鼠重新加载时预期的总横截面积增加被消除。这些结果表明，成熟成骨细胞中的Igf-1r在骨骼对机械负荷反应中的骨膜骨形成中起关键作用。
