ObjectiveTo explore the regulatory effect of 17β-estrodial on vitamin D receptor (VDR) expression in pre-osteoblasts and the involvement of MAPK signal pathway in the process. MethodsMC3T3-E1 subclone 14 cells were cultured in phenol-red free medium supplemented with 10% fetal bovine serum (FBS). Serum free medium was used when the cells were experimentally treated. After the cells were treated with 17β-estrodial for pre-determined time periods, expressions of vitamin D receptor (VDR) mRNA and protein were determined by SYBR green-based quantitative PCR and Western blotting analysis, respectively; and the activation of MAPK in MC3T3-E1 cells was examined by Western blotting analysis. Then the changes of VDR mRNA and protein in MC3T3-E1 cells were detected after the cells were treated with MAPKs inhibitors and 17β-estrodial. ResultsVDR mRNA and protein were upregulated in MC3T3-E1 cells after treatment with 17β-estrodial for 72 h. ERK/MAPK signal in MC3T3-E1 cells was activated within 15 min after treatment with 17β-estrodial and the activation remained for 60 min; but it did not activate JNK and p38 MAPK pathways. 17β-estrodial-induced VDR upregulation in MC3T3-E1 cells could be partly inhibited by ERK/MAPK inhibitor U0126. Conclusion17β-estrodial can upregulate VDR expression in osteoblasts and can rapidly activate MAPK signal pathway, which is involved in the estrogen-induced upregulation of VDR.