Skeletal unloading inhibits the in vitro proliferation and
differentiation of rat osteoprogenitor cells.
Kostenuik, Paul J., Bernard P. Halloran, Emily R. Morey-Holton, and
Daniel D. Bikle.
Veterans Administration Medical Center, San Francisco, CA 94121;
Department of Medicine, University of California, San Francisco,
California 94121., NASA-Ames Research Center, Moffett Field, CA
94035.
APStracts 4:0179E, 1997.
Loss 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 (BMCSs) 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 PCR of cDNA after
10, 15, 20, and 28 d 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 to
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.
Received 13 December 1996; accepted in final form 12 August 1997.
APS Manuscript Number E612-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997