AJP - Endocrinology and Metabolism, Vol 263, Issue 6 E1070-E1076, Copyright © 1992 by American Physiological Society
1,25(OH)2D3 blunts hormone-elevated cytosolic Ca2+ in osteoblast-like cells
J. Green, C. R. Kleeman, S. Schotland and L. H. Ye
Department of Medicine, University of California, School of Medicine, Los Angeles 90048.
Cytosolic free calcium ([Ca2+]i) is an important regulator of bone cell
physiology. We studied the interaction of vitamin D metabolites on the
hormonal-activated Ca message system in the osteoblastic cell line UMR-106.
The acute rise in [Ca2+]i induced by different calciotropic hormones
[parathyroid hormone, prostaglandin E2 (PGE2)] was dose dependently blunted
by 1,25-dihydroxyvitamin D [1,25(OH)2D3; half-maximal inhibitory concn
approximately 5 x 10(-11) M] and was initially observed after 8 h of
preincubation. The 1,25(OH)2D3 metabolite of vitamin D was two orders of
magnitude more potent than 24,25(OH)2D3 and 25(OH)D3. To discern between an
effect of 1,25(OH)2D3 on hormonal-induced Ca2+ entry through the plasma
membrane channel vs. release of Ca2+ from internal stores, we suspended
fura-2-loaded cells in Mn2+ rather than Ca2+ buffers. In cells preincubated
with 1,25(OH)2D3, [Ca2+]i release (indicated by [Ca2+]i transient) was
significantly blunted, whereas Mn2+ influx (indicating Ca2+ flux across the
plasma membrane) was unaltered, suggesting a selective effect of
1,25(OH)2D3 on hormonal-activated release of Ca2+ from intracellular
stores. 1,25(OH)2D3 also inhibited the PGE2-induced production of inositol
1,4,5-trisphosphate. We conclude that, in osteoblasts, chronic (hours)
incubation with 1,25(OH)2D3 leads to attenuated stimulation of the [Ca2+]i
transduction pathway by calciotropic hormones. This effect of 1,25(OH)2D3
may provide a cellular basis for the synergism between the effects of
vitamin D and calciotropic hormones at the bone level.
