Conditional expression of constitutively active estrogen receptor α in osteoblasts increases bone mineral density in mice.

Estrogen plays an important role in maintaining bone density in women. Estrogen receptor (ER) is expressed in osteoblasts and osteoclasts; however, the precise mechanism of ER in bone is not fully understood. In the present study, we generated a conditional transgenic mouse caERα(ColI) that expresses the constitutively active ERα in osteoblasts using collagen type I promoter-driven Cre transgenic mice. The caERα(ColI) mice showed increased bone mineral density (BMD). Osteoblasts prepared from caERα(ColI) mice expressed high levels of osteoprotegerin and decreased levels of IL-6, both of which are known to regulate osteoclast differentiation. These results suggest that ERα regulates osteoprotegerin and IL-6 production in osteoblasts and modulates BMD. The conditional transgenic mouse model is useful for understanding the in vivo function of ERα.