A synergetic role of 1,25-dihydroxyvitamin D(3) in 17β-estradial induced-proliferation and differentiation of osteoblastic MC3T3-E1 cells.
Although the effect of 17β-estradial, a polyphenolic phytoestrogen, on bone cell function has been studied in numerous cell models, the synergetic role of 1, 25-dihydroxyvitamin D(3) on 17β-estradial induced-proliferation and differentiation of osteoblastic cells, and the underlying mechanism are obscure. Here, we investigated the in vitro effect of 17β-estradial on cell proliferation and osteoblastic maturation in MC3T3-E1 cells. 17β-estradial could promote the proliferation and viability of MC3T3-E1 cells, associated with upregulation of cyclin E and proliferation cell nuclear antigen (PCNA) mRNA expression, and downregulation of cyclin-dependent kinase inhibitor 2b (Cdkn2b) mRNA expression. Moreover, 17β-estradial also could stimulate osteoblastic differentiation and bone formation as assessed by alkaline phosphatase (ALP) and Alizarin Red S staining, through induction of the expression of osteoblastic markers, including ALP, osteopontin and type I collagen in MC3T3-E1 cells. However, 1,25-dihydroxyvitamin D(3) treatment alone showed no effect on proliferation and differentiation of MC3T3-E1 cells, but could coordinately augment effects of 17β-estradial on MC3T3-E1 cells. The mechanism conducted demonstrated that 17β-estradial activated ERK1/2 but not JNK and p38, and U0126, an ERK1/2 pathway inhibitor, significantly downregulated vitamin D receptor expression induced by 17β-estradial in MC3T3-E1 cells. Thus, our data demonstrated a synergistical role of 1,25-dihydroxyvitamin D(3) and 17β-estradial in proliferation and differentiation of osteoblasts, and this coordinated regulation might depend on the upregulation of vitamin D receptor in osteoblasts by 17β-estradial. Moreover, during the process of vitamin D receptor upregulation by 17β-estradial, ERK1/2 signaling is involved.
Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Lige
L
Song
Xiuzhen
X
Zhang
Yun
Y
Zhou
D016475:3T3 Cells; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D004958:Estradiol; D002117:Calcitriol