Abstract 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 Igf-1 receptor deficient (Igf-1r −/−) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r −/− mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r +/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r −/− 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 Igf-1r −/− 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.
Highlights ► We tested the response of osteoblast-specific Igf-1r−/− mice to unloading/reloading. ► Increased periosteal bone formation with reloading is blocked in Igf-1r −/− mice. ► Increased cortical bone expansion with reloading is inhibited in Igf-1r −/− mice. ► Igf-1r in mature osteoblasts mediates reloading-induced periosteal bone formation.
Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading
Acta Astronautica ; 92 , 1 ; 73-78
2012-08-04
6 pages
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch