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Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

Ikeda, Kazuhiro, Tsukui, Tohru, Imazawa, Yukiko, Horie-Inoue, Kuniko, Inoue, Satoshi
Biochemical and biophysical research communications 2012 v.425 no.4 pp. 912-917
chondrocytes, collagen, estrogen receptors, genetically modified organisms, growth plate, in situ hybridization, mice, mutants, skeletal development, tibia
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 caERαCᵒˡᴵᴵ, expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERαCᵒˡᴵᴵ 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 caERαCᵒˡᴵᴵ mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERαCᵒˡᴵᴵ mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.