Age-dependent responsiveness of human female bone cells to vitamin D analog and PTH

Vitamin D less-calcemic analog JKF 1624 F2-2 (JKF) and PTH 1-34 stimulate in human female cultured osteoblasts (Ob) DNA synthesis (DNA), creatine kinase specific activity (CK), 1α, 25 vitamin D hydroxylase mRNA (1OHase) expression and 1,25(OH)2D3 (1,25) production, estrogen receptors (ER) mRNA expression and intracellular and membranal estrogen binding. In the present study, cultured Ob from different ages were subjected to hormonal stimulations and analyzed for different parameters. We found: 1) ERα expression is higher and ERβ expression is lower in pre-meno - pausal Ob (prOb), with similar intracellular and membranal binding. 2) JKF and PTH up-regulated ERα and JKF downregulated ERβ in both Ob, while PTH stimulated it in post- (poOb) and inhibited it in prOb. 3) There is higher expression of 1OHase mRNA in prOb, but 1,25 production is similar. Both parameters were hormonally stimulated to higher extent in prOb. 4) Ob express 12 and 15 lipoxygenase (LO) mRNA and produce 12- and 15-hydroxyeicosatetraenoic acid (H). 12LO expression is higher and 15LO is lower in prOb, while 12H is higher in prOb and 15H is similar in both. JKF inhibited 12LO expression in prOb and stimulated in poOb, whereas PTH stimulated it to higher extent in prOb. JKF stimulated and PTH inhibited 15LO expression in both; 12 and 15H were stimulated by both hormones in both Ob. 5. PTH and JKF stimulated DNA and CK in both Ob. In conclusion Ob demonstrate some age-dependent response to calciotrophic hormones, but the mechanism and beneficial outcome for human is unclear.