Insulin‐like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

DD Bikle, T Sakata, C Leary, H Elalieh… - Journal of Bone and …, 2002 - academic.oup.com
DD Bikle, T Sakata, C Leary, H Elalieh, D Ginzinger, CJ Rosen, W Beamer, S Majumdar…
Journal of Bone and Mineral Research, 2002academic.oup.com
Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism (s) by
which it works remains imperfectly understood. Previous studies have indicated that PTH
stimulates insulin‐like growth factor (IGF) I production, but it remains uncertain whether IGF‐I
mediates some or all of the skeletal actions of PTH. To address this question, we examined
the skeletal response to PTH in IGF‐I‐deficient (knockout [k/o]) mice. These mice and their
normal littermates (NLMs) were given daily injections of PTH (80 μg/kg) or vehicle for 2 …
Abstract
Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin‐like growth factor (IGF) I production, but it remains uncertain whether IGF‐I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF‐I‐deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 μg/kg) or vehicle for 2 weeks after which their tibias were examined for fat‐free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild‐type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF‐I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several‐fold more in response to PTH than the mRNAs in the bones from their wild‐type littermates. These results indicate that IGF‐I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.
Oxford University Press