Osteogenic protein-1 down-regulates endothelin a receptors in
primary rat osteoblasts.
Kitten, Allison M., Stephen A. K. Harvey, Nick Criscimagna, Megan
Asher, John C. Lee, and Merle S. Olson .
Department of Biochemistry, University of Texas Health Science
Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7760
APStracts 4:0037E, 1997.
Osteogenesis is a complex process whereby growth factors and mediators
from both local and systemic sources modulate the bone forming
activities of osteoblasts. In the present study we utilized primary
cultures of fetal rat calvarial (FRC) cells to characterize
osteoblast responsiveness to the vascular mediator endothelin-1 (ET
-1) and to investigate whether ET-1 responses are regulated by
osteogenic protein-1 (OP-1). We found that a 1-2 day exposure to OP-1
diminished ET-1 receptor ligand binding and signal transduction by
down-regulating ET-1 receptor mRNA expression. ET-1-mediated calcium
signaling and ligand binding were completely abolished by the ETA
receptor antagonist BQ-123, suggesting that ET-1 effects are mediated
by this receptor. Northern analysis of total RNA revealed that ETA
mRNA expression was inhibited 50% by OP-1 treatment whereas ETB
receptor mRNA was not detected by this method of analysis. In OP-1
-treated cultures, the magnitude and duration of ET-1 calcium signals
varied among individual cells. This finding may be related to a
heterogeneous OP-1 response, indicated by alkaline phosphatase
induction in only a subpopulation of cells. These results suggest
that modulation of osteoblast function by ET-1 occurs during distinct
periods of phenotypic development and imply that down-regulation of
ET-1 responsiveness may be necessary for optimal bone formation in
vivo.
Received 11 October 1996; accepted in final form 29 January 1997.
APS Manuscript Number E509-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 20 February 1997