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. 2018 Mar 15;2(4):217–226. doi: 10.1002/jbm4.10037

Figure 6.

Figure 6

Effects of estrogen are reversed in many, but not all, cases by inhibiting the sphingosine kinase. Representative estrogen‐sensitive mRNAs in human osteoblasts are shown. For RUNX2 (A), OSX (B), ALP (C), and S1PR1 (E), mRNA expressions were induced by 10 nM estradiol at 7 days. A 10‐μM SKi treatment reduced mRNA expression, and the combination of estradiol and SKi mRNA expression remained less than the control. The SPHK1 (D) mRNA expression was decreased by the sphingosine kinase inhibitor SKi, but was induced by estradiol with or without SKi. (F) Estradiol and S1P have different effects on the RANKL‐OPG pathway. Data shown are for 7‐day treatment. The untreated control is defined as 1.0. RANKL/OPG mRNA expression ratio was decreased 60% to 80% by 5 nM estradiol treatment and further by the sphingosine kinase inhibitor (10 μMSKi) treatment; the combination of SKi and estradiol gave an intermediate result. On the other hand, RANKL/OPG was not reduced in 200 nM S1P. Media were changed at 3‐day intervals. Duplicate results ± range; p values are relative to control = 1.0 except when indicated by bars.