ClC-3 chloride channels are involved in estradiol regulation of bone formation by MC3T3-E1 osteoblasts.

Evidence has been reported by us and others supporting the important roles of chloride channels in a number of osteoblast cell functions. The ClC-3 chloride channel is activated by estradiol binding to estrogen receptor alpha on the cell membranes of osteoblasts. However, the functions of these chloride channels in estrogen regulation of osteoblast metabolism remain unclear. In the present study, the roles of chloride channels in estrogen regulation of osteoblasts were investigated in the osteoblastic cell line MC3T3-E1. Estrogen 17β-estradiol enhanced collagen I protein expression, alkaline phosphatase activity, and mineralization were inhibited, by chloride channel blockers. Estradiol promoted ClC-3 chloride channel protein expression. Silencing of ClC-3 chloride channel expression prevented the elevation of osteodifferentiation in osteoblasts, which were regulated by estrogen. These data suggest that estrogen can regulate bone formation by activating ClC-3 chloride channels and the activation of ClC-3 chloride channels can enhance the osteodifferentiation in osteoblasts.