Itoh Shousaku, Udagawa Nobuyuki, Takahashi Naoyuki, Yoshitake Fumio, Narita Hiroko, Ebisu Shigeyuki, Ishihara Katsuhiko
Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
Bone. 2006 Sep;39(3):505-12. doi: 10.1016/j.bone.2006.02.074. Epub 2006 May 6.
Signal transduction and activator of transcription (Stat) 3 is a transcription factor that is activated by a variety of cytokines and growth factors, including IL-6 family cytokines. These cytokines regulate bone homeostasis and have been reported to regulate the differentiation of osteoblasts and osteoclasts through Stat3 activation in vitro, but the in vivo physiological role of Stat3 in bone homeostasis is unknown. Here, we report that gp130 knock-in mice gp130(F759/F759), in which IL-6 family cytokine-mediated Stat3 activation is enhanced, showed an osteosclerotic phenotype. To further clarify the role of Stat3 in bone formation, we generated mice with osteoblast-specific disruption of the Stat3 gene via the Cre-LoxP recombination system using alpha1(I)-collagen promoter Cre transgenic mice. The alpha1(I)Cre;Stat3(flox/-) mice showed an osteoporotic phenotype because of a reduced bone formation rate. Thus, the Stat3 signal in osteoblasts plays a pivotal role in bone formation in vivo.
信号转导及转录激活因子（Stat）3是一种转录因子，可被多种细胞因子和生长因子激活，包括IL-6家族细胞因子。这些细胞因子调节骨稳态，并且据报道在体外通过Stat3激活来调节成骨细胞和破骨细胞的分化，但Stat3在骨稳态中的体内生理作用尚不清楚。在此，我们报道gp130基因敲入小鼠gp130（F759/F759）表现出骨硬化表型，在该小鼠中IL-6家族细胞因子介导的Stat3激活增强。为了进一步阐明Stat3在骨形成中的作用，我们使用α1（I）-胶原启动子Cre转基因小鼠，通过Cre-LoxP重组系统构建了成骨细胞特异性Stat3基因缺失的小鼠。α1（I）Cre；Stat3（flox/-）小鼠由于骨形成率降低而表现出骨质疏松表型。因此，成骨细胞中的Stat3信号在体内骨形成中起关键作用。
