Title

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

Document Type

Article

Publication Date

2002

Keywords

Animals, Bone-Density, Bone-and-Bones, Collagen, Heterozygote, Homozygote, Insulin-Like-Growth-Factor-I, Male, Mice, Mice-Knockout, Osteoblasts, Osteocalcin, Osteogenesis, Parathyroid-Hormone, RNA-Messenger, Receptor-IGF-Type-1, Receptors-Parathyroid-Hormone

JAX Source

J Bone Miner Res 2002 Sep; 17(9):1570-8.

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 microg/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.

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