AJP - Endocrinology and Metabolism, Vol 263, Issue 6 E1113-E1118, Copyright © 1992 by American Physiological Society
Dose-dependent effects of aluminum on osteocalcin synthesis in osteoblast-like ROS 17/2 cells in culture
P. Fanti, M. S. Kindy, S. Mohapatra, J. Klein, G. Colombo and H. H. Malluche
Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington 40536.
This in vitro study evaluates the effect of aluminum (Al3+) on osteocalcin,
a small protein that is produced by the osteoblast. After stimulation with
various doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-11) to 10(-9)
M], osteocalcin was consistently lower in the culture medium of ROS 17/2
osteoblastic cells conditioned with 5 microM Al(3+)-saturated transferrin
(AlTR) than in apotransferrin (ApoTR)-treated controls. In a second
experiment, cultures were conditioned with various doses of AlTR or ApoTR
(1.6-8.0 microM) and stimulated with 10(-9) M 1,25(OH)2D3. High doses of
AlTR (4.8-8.0 microM) resulted in lower medium and unchanged intracellular
content of osteocalcin than treatment with equal amounts of ApoTR. However,
in the same experiment, lower doses of AlTR or ApoTR (1.6 and 3.2 microM)
yielded different results, i.e., increased medium and intracellular
contents of osteocalcin in the Al(3+)-treated cells. Expression of
osteocalcin mRNA was not altered in cultures conditioned with low (1.6
microM) or high (8.0 microM) concentrations of AlTR or ApoTR. Similarly, no
effect of Al3+ was observed on total protein content, the rate of total
protein synthesis, and the degradation of secreted osteocalcin in cultures
conditioned with various doses of AlTR or ApoTR. These findings suggest
that AlTR affects osteocalcin synthesis in a specific manner, without
concomitant effects on the rate of total protein synthesis or on the rate
of degradation of osteocalcin. This effect is dose dependent, i.e., low
doses of AlTR stimulate and high doses suppress osteocalcin synthesis
and/or secretion, and it appears to be posttranscriptional, since the
expression of osteocalcin mRNA is not affected.
