A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation
A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation
复制标题
DOI：
10.1016/j.bone.2006.02.074
复制
发表时间：
2006-09-01
期刊：
影响因子：
4.1
通讯作者：
Ishihara, Katsuhiko
中科院分区：
文献类型：
--
作者：
Itoh, Shousaku;Udagawa, Nobuyuki;Ishihara, Katsuhiko
信号转导和转录激活因子（Stat）3是一种转录因子，可被多种细胞因子和生长因子（包括IL-6家族细胞因子）激活。这些细胞因子调节骨稳态，并已报道通过体外激活Stat 3来调节成骨细胞和破骨细胞的分化，但Stat 3在骨稳态中的体内生理作用尚不清楚。在这里，我们报告说，gp 130基因敲入小鼠gp 130（F759/F759），其中IL-6家族精氨酸介导的Stat 3激活增强，表现出骨质疏松症表型。为了进一步阐明Stat 3在骨形成中的作用，我们使用α 1（I）-胶原启动子Cre转基因小鼠，通过Cre-LoxP重组系统产生了Stat 3基因成骨细胞特异性破坏的小鼠。由于骨形成率降低，α 1（I）Cre; Stat 3（flox/-）小鼠表现出骨质疏松表型。因此，成骨细胞中的Stat 3信号在体内骨形成中起着关键作用。(c)2006年爱思唯尔公司All rights reserved.
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 alpha 1(I)-collagen promoter Cre transgenic mice. The alpha 1(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. (c) 2006 Elsevier Inc. All rights reserved.