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Skeletal unloading inhibits the in vitro proliferation and differentiation of rat osteoprogenitor cellsLoss of weight bearing in the growing rat decreases bone formation, osteoblast numbers, and bone maturation in unloaded bones. These responses suggest an impairment of osteoblast proliferation and differentiation. To test this assumption, we assessed the effects of skeletal unloading using an in vitro model of osteoprogenitor cell differentiation. Rats were hindlimb elevated for 0 (control), 2, or 5 days, after which their tibial bone marrow stromal cells (BMSCs) were harvested and cultured. Five days of hindlimb elevation led to significant decreases in proliferation, alkaline phosphatase (AP) enzyme activity, and mineralization of BMSC cultures. Differentiation of BMSCs was analyzed by quantitative competitive polymerase chain reaction of cDNA after 10, 15, 20, and 28 days of culture. cDNA pools were analyzed for the expression of c-fos (an index of proliferation), AP (an index of early osteoblast differentiation), and osteocalcin (a marker of late differentiation). BMSCs from 5-day unloaded rats expressed 50% less c-fos, 61% more AP, and 35% less osteocalcin mRNA compared with controls. These data demonstrate that cultured osteoprogenitor cells retain a memory of their in vivo loading history and indicate that skeletal unloading inhibits proliferation and differentiation of osteoprogenitor cells in vitro.
Document ID
20040172813
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Kostenuik, P. J.
(Veterans Administration Medical Center, University of California Department of Medicine, San Francisco 94121, United States)
Halloran, B. P.
Morey-Holton, E. R.
Bikle, D. D.
Date Acquired
August 22, 2013
Publication Date
December 1, 1997
Publication Information
Publication: The American journal of physiology
Volume: 273
Issue: 6 Pt 1
ISSN: 0002-9513
Subject Category
Aerospace Medicine
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Musculoskeletal
Non-NASA Center
NASA Center ARC

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