Details

Autor(en) / Beteiligte

• Rao, L G
• Liu, LJ-F
• Rawlins, M R
• McBroom, R J
• Murray, T M
• Reddy, G S
• Uskokovic, M R
• Rao, D S
• Sutherland, M K

Titel

The Biological Activities of 1 alpha ,25-Dihydroxyvitamin D sub(3) and Its Synthetic Analog 1 alpha ,25-Dihydroxy-16-ene-vitamin D sub(3) in Normal Human Osteoblastic Cells and Human Osteosarcoma SaOS-2 Cells Are Modulated by 17- beta Estradiol and Dependent on Stage of Differentiation

Ist Teil von

• Biological & pharmaceutical bulletin, 2001-03, Vol.24 (3), p.242-248

Erscheinungsjahr

2001

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• We compared the effects of 1 alpha ,25-dihydroxyvitamin D sub(3) [1 alpha ,25(OH) sub(2)D sub(3)] and its analog, 1 alpha ,25-dihydroxy-16-ene-vitamin D sub(3) [1 alpha ,25(OH) sub(2)-16-ene-D sub(3)], as well as their interactions with 17- beta estradiol (E sub(2)) on osteoblastic function in our human normal (HOB) and osteosarcoma SaOS-2 cell models representing two different stages of differentiation, the more differentiated HOB+DEX cells and SaOS+DEX cells, and the corresponding less differentiated HOB-DEX and SaOS-DEX cells. The differential effects of 1 alpha ,25(OH) sub(2)D sub(3) and 1 alpha ,25(OH) sub(2)-16-ene-D sub(3) and the modulation by E sub(2) on ALP activity in HOB-DEX and HOB+DEX cells were small but significant. The most significant effects were seen in SaOS+DEX cells, in which 1 alpha ,25(OH) sub(2)-16-ene-D sub(3) was 100-fold more potent than 1 alpha ,25(OH) sub(2)D sub(3), the maximal enhancement being exerted at 0.1 nM and 10 nM, respectively. E sub(2) enhanced the stimulatory effects of both compounds, with ALP being increased 2-fold at 0.1 nM (p<0.001). Osteocalcin (OC) production in HOB-DEX cells was stimulated 1.3 to 1.4-fold by 1 alpha ,25(OH) sub(2)D sub(3) and 1 alpha ,25(OH) sub(2)-16-ene-D sub(3) at a concentration of 0.01 nM, with E sub(2) inhibiting the effect of 1 alpha ,25(OH) sub(2)-16-ene-D sub(3). In SaOS-DEX and SaOS+DEX cells, 1 alpha ,25(OH) sub(2)D sub(3) and 1 alpha ,25(OH) sub(2)-16-ene-D sub(3) stimulated OC production 1.6-fold at 0.1 nM with E sub(2) slightly enhancing the effect of 1 alpha ,25(OH) sub(2)D sub(3). Western blot analysis of 1 alpha ,25(OH) sub(2)D sub(3) receptor (VDR) levels showed that in SaOS+DEX cells, the effect of 1 alpha ,25(OH) sub(2)D sub(3) was larger than that of 1 alpha ,25(OH) sub(2)-16-ene-D sub(3). These results show that 1 alpha ,25(OH) sub(2)-16-ene-D sub(3) is biologically active in human osteoblasts.