Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Biochem Biophys Res Commun. 2012 Sep 7;425(4):912-7. doi: 10.1016/j.bbrc.2012.07.170. Epub 2012 Aug 9.
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 caERα(ColII), expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα(ColII) 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 caERα(ColII) mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα(ColII) mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.
雌激素在调节软骨细胞增殖和分化方面发挥着重要作用，这是长骨生长的必要步骤；然而，雌激素对软骨细胞作用的机制尚未完全阐明。在本研究中，我们利用软骨细胞特异性 II 型胶原启动子驱动的 Cre 转基因小鼠，生成了条件性转基因小鼠，命名为 caERα(ColII)，在软骨细胞中表达组成型激活的突变雌激素受体 (ER)α。caERα(ColII) 小鼠表现出纵向生长迟缓，骨长度缩短。BrdU 标记显示 caERα(ColII) 小鼠胫骨生长板增殖层中肥大软骨细胞的增殖减少。原位杂交分析显示，caERα(ColII) 小鼠中肥大软骨细胞的成熟受损。这些结果表明，ERα 是骨骼发育过程中软骨细胞增殖和成熟的关键调节因子，介导体内长骨生长。
