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Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse boneParathyroid 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.
Document ID
20040088145
Document Type
Reprint (Version printed in journal)
Authors
Bikle, Daniel D. (Veterans Affairs Medical Center and University of California San Francisco 94121, United States)
Sakata, Takeshi
Leary, Colin
Elalieh, Hashem
Ginzinger, David
Rosen, Clifford J.
Beamer, Wesley
Majumdar, Sharmila
Halloran, Bernard P.
Date Acquired
August 21, 2013
Publication Date
September 1, 2002
Publication Information
Publication: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume: 17
Issue: 9
ISSN: 0884-0431
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: R01 DK54793
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Musculoskeletal