Modulation of ecto-nucleoside triphosphate pyrophosphatase activity of human osteoblast-like bone cells by 1α,25-dihydroxy vitamin D3, 24R,25-dihydroxyvitamin D3, parathyroid hormone, and dexamethasone

Babatunde O. Oyajobi, R. Graham G Russell, Alison M. Caswell

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19 Citations (Scopus)

Abstract

Original languageEnglish
Pages (from-to)1259-1266
Number of pages8
JournalJournal of Bone and Mineral Research
Volume9
Issue number8
StatePublished - Aug 1994
Externally publishedYes

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Pyrophosphatases
Parathyroid Hormone
Osteoblasts
Human Activities
Dexamethasone
Bone and Bones
Cholecalciferol
Enzymes
Teriparatide
Bone Remodeling
Cycloheximide
Glucocorticoids
nucleoside triphosphate pyrophosphatase
dihydroxy-vitamin D3
Fibroblasts
Skin

ASJC Scopus subject areas

  • Surgery

Cite this

@article{87516c95168f44b9b2cb4db7670693b2,
title = "Modulation of ecto-nucleoside triphosphate pyrophosphatase activity of human osteoblast-like bone cells by 1α,25-dihydroxy vitamin D3, 24R,25-dihydroxyvitamin D3, parathyroid hormone, and dexamethasone",
abstract = "Extracellular inorganic pyrophosphate (PPi) is involved in the regulation of mineralization, and there is evidence that the cell surface enzyme, NTP pyrophosphatase, is a major source of this metabolite in bone. Osteotrophic agents that influence bone turnover may exert their effects, in part, by modulating the activity of ecto-NTP pyrophosphatase in bone cells. We investigated the effect of 1,25(OH)2D3,24,25(OH)2D3, dexamethasone, and parathyroid hormone (PTH) on the activity of this enzyme in cultured human trabecular bone-derived osteoblast-like cells. 1,25(OH)2D3 at 10-11-10-9 M induced a dose- and time-dependent increase in activity (at 96 h; maximum 10-9 M, p < 0.001), whereas higher concentrations (10-8 and 10-7 M) had no effect. In contrast, 24,25(OH)2D3 was effective only at 10-8 and 10-6 M (at 96 h; p < 0.01). Dexamethasone (10-9-10-7 M) caused a dose-dependent decrease in ecto-NTP pyrophosphatase activity (10-7 M, p < 0.001); concentrations higher than 10-7 M did not evoke greater inhibition. This effect became apparent by 48 h and was significantly enhanced after 72 h. The response to dexamethasone was attenuated by cycloheximide, indicating a requirement for de novo protein synthesis. Interestingly, the stimulatory effect of 10-9 M 1,25(OH)2D3 on ecto-NTP pyrophosphatase activity was significantly enhanced in the presence of dexamethasone (10-9-10-7 M). Human PTH(1-34) and bovine PTH(1-34) in the range 10-10-10-7 M had no effect on enzyme activity over a 72 h period. The effects of vitamin D3 on the expression of bone ecto-NTP pyrophosphatase may be tissue or cell type specific because the ecto-NTP pyrophosphatase activity of subject-matched skin-derived fibroblasts showed no sensitivity to 1,25(OH)2D3. These data suggest a possible role for both vitamin D3 metabolites and glucocorticoids in the regulation of the mineralization process in vivo via modulation of PPi production.",
author = "Oyajobi, {Babatunde O.} and Russell, {R. Graham G} and Caswell, {Alison M.}",
year = "1994",
month = "8",
language = "English",
volume = "9",
pages = "1259--1266",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
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TY - JOUR

T1 - Modulation of ecto-nucleoside triphosphate pyrophosphatase activity of human osteoblast-like bone cells by 1α,25-dihydroxy vitamin D3, 24R,25-dihydroxyvitamin D3, parathyroid hormone, and dexamethasone

AU - Oyajobi, Babatunde O.

AU - Russell, R. Graham G

AU - Caswell, Alison M.

PY - 1994/8

Y1 - 1994/8

N2 - Extracellular inorganic pyrophosphate (PPi) is involved in the regulation of mineralization, and there is evidence that the cell surface enzyme, NTP pyrophosphatase, is a major source of this metabolite in bone. Osteotrophic agents that influence bone turnover may exert their effects, in part, by modulating the activity of ecto-NTP pyrophosphatase in bone cells. We investigated the effect of 1,25(OH)2D3,24,25(OH)2D3, dexamethasone, and parathyroid hormone (PTH) on the activity of this enzyme in cultured human trabecular bone-derived osteoblast-like cells. 1,25(OH)2D3 at 10-11-10-9 M induced a dose- and time-dependent increase in activity (at 96 h; maximum 10-9 M, p < 0.001), whereas higher concentrations (10-8 and 10-7 M) had no effect. In contrast, 24,25(OH)2D3 was effective only at 10-8 and 10-6 M (at 96 h; p < 0.01). Dexamethasone (10-9-10-7 M) caused a dose-dependent decrease in ecto-NTP pyrophosphatase activity (10-7 M, p < 0.001); concentrations higher than 10-7 M did not evoke greater inhibition. This effect became apparent by 48 h and was significantly enhanced after 72 h. The response to dexamethasone was attenuated by cycloheximide, indicating a requirement for de novo protein synthesis. Interestingly, the stimulatory effect of 10-9 M 1,25(OH)2D3 on ecto-NTP pyrophosphatase activity was significantly enhanced in the presence of dexamethasone (10-9-10-7 M). Human PTH(1-34) and bovine PTH(1-34) in the range 10-10-10-7 M had no effect on enzyme activity over a 72 h period. The effects of vitamin D3 on the expression of bone ecto-NTP pyrophosphatase may be tissue or cell type specific because the ecto-NTP pyrophosphatase activity of subject-matched skin-derived fibroblasts showed no sensitivity to 1,25(OH)2D3. These data suggest a possible role for both vitamin D3 metabolites and glucocorticoids in the regulation of the mineralization process in vivo via modulation of PPi production.

AB - Extracellular inorganic pyrophosphate (PPi) is involved in the regulation of mineralization, and there is evidence that the cell surface enzyme, NTP pyrophosphatase, is a major source of this metabolite in bone. Osteotrophic agents that influence bone turnover may exert their effects, in part, by modulating the activity of ecto-NTP pyrophosphatase in bone cells. We investigated the effect of 1,25(OH)2D3,24,25(OH)2D3, dexamethasone, and parathyroid hormone (PTH) on the activity of this enzyme in cultured human trabecular bone-derived osteoblast-like cells. 1,25(OH)2D3 at 10-11-10-9 M induced a dose- and time-dependent increase in activity (at 96 h; maximum 10-9 M, p < 0.001), whereas higher concentrations (10-8 and 10-7 M) had no effect. In contrast, 24,25(OH)2D3 was effective only at 10-8 and 10-6 M (at 96 h; p < 0.01). Dexamethasone (10-9-10-7 M) caused a dose-dependent decrease in ecto-NTP pyrophosphatase activity (10-7 M, p < 0.001); concentrations higher than 10-7 M did not evoke greater inhibition. This effect became apparent by 48 h and was significantly enhanced after 72 h. The response to dexamethasone was attenuated by cycloheximide, indicating a requirement for de novo protein synthesis. Interestingly, the stimulatory effect of 10-9 M 1,25(OH)2D3 on ecto-NTP pyrophosphatase activity was significantly enhanced in the presence of dexamethasone (10-9-10-7 M). Human PTH(1-34) and bovine PTH(1-34) in the range 10-10-10-7 M had no effect on enzyme activity over a 72 h period. The effects of vitamin D3 on the expression of bone ecto-NTP pyrophosphatase may be tissue or cell type specific because the ecto-NTP pyrophosphatase activity of subject-matched skin-derived fibroblasts showed no sensitivity to 1,25(OH)2D3. These data suggest a possible role for both vitamin D3 metabolites and glucocorticoids in the regulation of the mineralization process in vivo via modulation of PPi production.

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