Effects of 1alpha,25-dihydroxy-16ene, 23yne-vitamin D3 on osteoblastic function in human osteosarcoma SaOS-2 cells: differentiation-stage dependence and modulation by 17-beta estradiol.

Abstract

We compared the separate effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) and its analog, 1alpha,25-dihydroxy-16ene,23yne-vitamin D3 (1alpha25(OH)2-16ene,23yne-D3), as well as their interactions with 17-beta estradiol (E2) 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 express higher PTH-stimulated adenylate cyclase (PTH-AC) and basal alkaline phosphatase (ALP) activities compared with SaOS-DEX cells. ALP: In SaOS+DEX cells, 0.1 nmol/L analog, but not 1alpha,25(OH)2D3, increased ALP activity 1.7-fold (p < 0.05). Instead, 1 nmol/L 1alpha,25(OH)2D3 increased ALP 1.4-fold (p < 0.05). In these cells, E2 enhanced 1alpha,25(OH)2D3-stimulated ALP activity (ANOVA, F = 51.22, p <0.0001), while inhibiting the effect of the analog. [3H]-Thymidine uptake: In SaOS+DEX cells, 1alpha,25(OH)2D3 had biphasic effects (ANOVA, F = 13.08, p < 0.0001), which were not altered by E2. In contrast, the analog was stimulatory only with E2 (ANOVA, F = 3.59, p < 0.025). Osteocalcin (OC): 1alpha,25(OH)2D3 and its analog stimulated OC production in SaOS-DEX cells with smaller effects in SaOS+DEX cells. In SaOS-DEX cells, E2 enhanced the effect of 1alpha,25(OH)2D3, but not that of the analog. PTH-AC: In SaOS-DEX cells, 100 nmol/L analog inhibited PTH-AC activities by 50% (p < 0.01), whereas 1alpha,25(OH)2D3 had little effect. In SaOS+DEX cells, both compounds inhibited PTH-AC approximately 35%. E2 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 1alpha,25(OH)2-16ene,23yne-D3 was effective in regulating osteoblastic function; its effects were modulated by E2 and dependent upon the stage of osteoblast differentiation.

• Authors: L G Rao, M K Sutherland, G S Reddy, M L Siu-Caldera, M R Uskokovic, T M Murray
• Journal: Bone (Bone) Vol. 19 Issue 6 Pg. 621-7 (Dec 1996) ISSN: 8756-3282 [Print] United States
• PMID: 8968029 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dihydroxycholecalciferols
• Parathyroid Hormone
• Osteocalcin
• Estradiol
• 1 alpha,24-dihydroxyvitamin D3
• Alkaline Phosphatase
• Adenylyl Cyclases
• Calcitriol
• Ro 23-7553
• Thymidine

Topics

• Adenylyl Cyclases (metabolism)
• Alkaline Phosphatase (metabolism)
• Calcitriol (analogs & derivatives, pharmacology)
• Cell Differentiation
• Dihydroxycholecalciferols (pharmacology)
• Estradiol (pharmacology)
• Humans
• Osteoblasts (drug effects, metabolism)
• Osteocalcin (biosynthesis, drug effects)
• Osteosarcoma
• Parathyroid Hormone (pharmacology)
• Thymidine (metabolism)
• Tumor Cells, Cultured