Adrenomedullin is a potent stimulator of osteoblastic activity in
vitro and in vivo.
Cornish, Jillian, Karen E Callon, David H Coy, Ning-Yi Jiang, Liqun
Xiao, Garth Js Cooper, Ian R Reid.
Department of Medicine and School of Biological Sciences,
University of Auckland, Auckland, New Zealand. Peptide Research
Laboratories, Tulane University Medical Center, New Orleans, USA.
APStracts 4:0192E, 1997.
Adrenomedullin is a 52-amino acid, vasodilator peptide produced in
many tissues, including bone. It has 20% sequence identity with
amylin, a regulator of osteoblast growth, and circulates in picomolar
concentrations. The present study assesses whether adrenomedullin
also acts on osteoblasts.At concentrations of 10-12M and greater,
adrenomedullin produced a dose-dependent increase in cell number and
[3H]-thymidine incorporation in cultures of fetal rat osteoblasts.
This effect was also seen with adrenomedullin(15-52), -(22-52), and
-(27-52) but adrenomedullin(40-52) was inactive. These effects were
lost in the presence of amylin blockers, suggesting they were
mediated by the amylin receptor. Adrenomedullin also increased [3H]
-thymidine incorporation into cultured neonatal mouse calvariae but,
unlike amylin, did not reduce bone resorption in this model. It
stimulated phenylalanine incorporation into both isolated osteoblasts
and calvariae. When injected daily for 5 days over the calvariae of
adult mice, it increased indices of bone formation 2- to 3-fold (P
< 0.0001) and increased mineralized bone area by 14% (P = 0.004).
It is concluded that adrenomedullin regulates osteoblast function and
that it increases bone mass in vivo. The potential of this family of
peptides in the therapy of osteoporosis should be further evaluated.
Received 10 April 1997; accepted in final form 19 August 1997.
APS Manuscript Number E163-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 September 1997