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Modulation of ecto‐nucleoside triphosphate pyrophosphatase activity of human osteoblast‐like bone cells by 1α,25‐dihydroxyvitamin D 3 , 24 R , 25‐dihydroxyvitamin D 3 , parathyroid hormone, and dexamethasone
Author(s) -
Oyajobi Babatunde O.,
Russell R. Graham G.,
Caswell Alison M.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090816
Subject(s) - endocrinology , medicine , parathyroid hormone , osteoblast , pyrophosphatase , cycloheximide , pyrophosphate , extracellular , chemistry , calcitriol , bone cell , bone resorption , calcium , enzyme , biology , biochemistry , in vitro , protein biosynthesis
Extracellular inorganic pyrophosphate (PP i ) 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) 2 D 3 ,24,25(OH) 2 D 3 , dexamethasone, and parathyroid hormone (PTH) on the activity of this enzyme in cultured human trabecular bone‐derived osteoblast‐like cells. 1,25(OH) 2 D 3 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) 2 D 3 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) 2 D 3 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 D 3 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) 2 D 3 . These data suggest a possible role for both vitamin D 3 metabolites and glucocorticoids in the regulation of the mineralization process in vivo via modulation of PP i production.