EFFECTS OF 1-ALPHA,25-DIHYDROXY-16ENE, 23YNE-VITAMIN-D-3 ON OSTEOBLASTIC FUNCTION IN HUMAN OSTEOSARCOMA SAOS-2 CELLS - DIFFERENTIATION-STAGE DEPENDENCE AND MODULATION BY 17-BETA ESTRADIOL
Lg. Rao et al., EFFECTS OF 1-ALPHA,25-DIHYDROXY-16ENE, 23YNE-VITAMIN-D-3 ON OSTEOBLASTIC FUNCTION IN HUMAN OSTEOSARCOMA SAOS-2 CELLS - DIFFERENTIATION-STAGE DEPENDENCE AND MODULATION BY 17-BETA ESTRADIOL, Bone, 19(6), 1996, pp. 621-627
We compared the separate effects of 1 alpha,25-dihydroxyvitamin D-3 (1
alpha,25(OH)(2)D-3) and its analog, 1 alpha,25-dihydroxy-16ene,23yne-
vitamin D-3 (1 alpha 25(OH)(2)-16ene,23yne-D-3), as well as their inte
ractions with 17-beta estradiol (E(2)) in our human osteosarcoma SaOS-
2 cell models representing two stages of differentiation, the SaOS+DEX
and SaOS-DEX cells, SaOS+DEX cells have been previously shown to expr
ess higher PTH-stimulated adenylate cyclase (PTH-AC) and basal alkalin
e phosphatase (ALP) activities compared with SaOS-DEX cells, ALP: In S
aOS+DEX cells, 0.1 nmol/L analog, but not 1 alpha,25(OH)(2)D-3, increa
sed ALP activity 1.7-fold (p < 0.05), Instead, 1 nmol/L 1 alpha,25(OH)
(2)D-3 increased ALP 1.4-fold (p < 0.05), In these cells, E(2) enhance
d 1 alpha,25(OH)(2)D-3-stimulated ALP activity (ANOVA, F = 51.22, p <
0.0001), while inhibiting the effect of the analog, [H-3]-Thymidine up
take: In SaOS+DEX cells, 1 alpha,25(OH)(2)D-3 had biphasic effects (AN
OVA, F = 13.08, p < 0.0001), which were not altered by E(2), In contra
st, the analog was stimulatory only with E(2) (ANOVA, F = 3.59, p < 0.
025), Osteocalcin (OC): 1 alpha,25(OH)(2)D-3 and its analog stimulated
OC production in SaOS-DEX cells with smaller effects in SaOS+DEX cell
s, In SaOS-DEX cells, E(2) enhanced the effect of 1 alpha,25(OH)(2)D-3
, but not that of the analog, PTH-AC: In SaOS-DEX cells, 100 nmol/L an
alog inhibited PTH-AC activities by 50% (p < 0.01), whereas 1 alpha,25
(OH)(2)D-3 had little effect, In SaOS+DEX cells, both compounds inhibi
ted PTH-AC similar to 35%, E(2) inhibited the effect of the analog in
SaOS-DEX cells, but enhanced the effects of both compounds in SaOS+DEX
cells, These results show that the analog 1 alpha,25(OH)(2)-16ene,23y
ne-D-3 was effective in regulating osteoblastic function; its effects
were modulated by E(2) and dependent upon the stage of osteoblast diff
erentiation. (C) 1996 by Elsevier Science Inc.