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Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expressionA mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.
Document ID
20040088321
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Lotinun, Sutada
(Mayo Clinic Rochester, MN 55905, United States)
Sibonga, Jean D.
Turner, Russell T.
Date Acquired
August 21, 2013
Publication Date
February 1, 2002
Publication Information
Publication: Endocrine
Volume: 17
Issue: 1
ISSN: 0969-711X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AA11140
Distribution Limits
Public
Copyright
Other
Keywords
Review
Non-NASA Center
NASA Discipline Regulatory Physiology
Review, Tutorial

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