title: Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading.
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-specificIgf-1 receptordeficient (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 inIgf-1r+/+mice. However, the recovery of periosteal bone formation with reloading was completely inhibited inIgf-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 inIgf-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.
authors: 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.
authors: Takuo
authors: T
authors: Kubota
authors: Hashem Z
authors: HZ
authors: Elalieh
authors: Neema
authors: N
authors: Saless
authors: Chak
authors: C
authors: Fong
authors: Yongmei
authors: Y
authors: Wang
authors: Muriel
authors: M
authors: Babey
authors: Zhiqiang
authors: Z
authors: Cheng
authors: Daniel D
authors: DD
authors: Bikle
keywords: Insulin-like growth factor 1 receptor; osteoblasts; periosteal bone formation; reloading; unloading
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