Cgmp produced in response to anp and cnp regulates the
proliferation and differentiation of osteoblastic cells.
Hagiwara, Hiromi, Atsuto Inoue, Akira Yamaguchi, Satoshi Yokose,
Mayumi Furuya, Shoji Tanaka, and Shigehisa Hirose.
Research Center for Experimental Biology and Department of
Biological Sciences, Tokyo Institute of Technology, 4259 Nagatsuta
-cho, Midori-ku, Yokohama 226; Department of Oral Pathology, School of
Dentistry, Showa University, Hatanodai, Tokyo 142; Suntory Institute
for Biomedical Research, Shimamoto, Mishima, Osaka 618, Japan
APStracts 2:0435C, 1995.
The effects of natriuretic peptides on the proliferation and
differentiation of osteoblast-like cells from rat calvariae were
examined. Natriuretic peptides are physiological agonists that
activate receptor guanylate cyclases, namely, natriuretic peptide
receptor-A (NPR-A) and -B (NPR-B). Exposure of cells to atrial
natriuretic peptide (ANP) and C-type natriuretic peptide (CNP)
resulted in large increases in the rate of intracellular production
of cGMP. Moreover, CNP-like immunoreactivity was detected in the
conditioned medium from osteoblast-like cells, while ANP was
undetectable. In cells exposed to natriuretic peptides, a dose
-dependent reduction in the rate of DNA synthesis was observed.
Natriuretic peptides also stimulated the activity of ALPase and the
expression of mRNA for ALPase and osteocalcin and the mineralization
of nodules by the cultured cells. These results could be reproduced
by treating cells with 8-bromo-cGMP (8-Br-cGMP). Endothelin-1 (ET-1),
whose physiological functions are the opposite of those of
natriuretic peptides, decreased the ALPase activity and the
mineralization of nodules. In the present study, natriuretic peptides
were demonstrated to promote bone formation via the action of cGMP in
a signal-transduction pathway mediated by specific receptors in
osteoblast-like cells.
Received 7 August 1995; accepted in final form 27 November 1995.
APS Manuscript Number C483-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95