Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER alpha(ColII), expressing constitutively active mutant estrogen receptor (ER) alpha in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER alpha(ColIII) mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER alpha(ColIII) mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER alpha(ColII) mice. These results suggest that ER alpha is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo. (C) 2012 Elsevier Inc. All rights reserved.