Additive effects of acidosis and parathyroid hormone on mouse
osteoblast and osteoclast function.
Bushinsky, David A., and Erica L. Nilsson.
Nephrology Unit University of Rochester School of Medicine,
Rochester, NY 14642
APStracts 2:0213C, 1995.
Patients with end stage renal disease are acidotic and often develop
secondary hyperparathyroidism. Whether acidosis contributes to the
bone disease observed in these patients is not clear. To determine
whether acidosis and PTH have additive effects on net calcium flux
(JCa) from bone and on bone cell function we measured JCa,
osteoblastic collagen synthesis and osteoclastic [beta]-glucuronidase
release from neonatal mouse calvariae cultured in control (Ctl, pH
nearly equal to 7.4) or acidified (Met, pH nearly equal to 7.1)
medium with or without a submaximal concentration of PTH (10-10M) for
48 h. When compared to Ctl, from 24-48 h JCa was increased with Met
and with PTH and the combination of Met+PTH increased JCa further.
When compared to Ctl, collagen synthesis was decreased with Met and
with PTH and decreased further with Met+PTH. There was an inverse
correlation between percent collagen synthesis and JCa. When compared
to Ctl, [beta]-glucuronidase release into the medium was increased
with Met and with PTH and increased further with Met+PTH. There was a
direct correlation between medium [beta]-glucuronidase activity and
JCa. Osteoclastic [beta]-glucuronidase activity was correlated
inversely with osteoblastic collagen synthesis. During cultures to 96
h there continued to be greater JCa from calvariae incubated with
Met+PTH than either treatment alone. Thus acidosis and PTH
independently stimulated JCa from bone, inhibited osteoblastic
collagen synthesis and stimulated osteoclastic [beta]-glucuronidase
secretion while the combination had a greater effect on each of these
parameters than either treatment alone. These findings indicate that
acidosis and PTH can have an additive effect on bone cell function
and suggest that uremic osteodystrophy may result from a combination
of a low pH and an elevated PTH.
Received 16 February 1995; accepted in final form 18 May 1995.
APS Manuscript Number C92-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.