Stat1 functions as a attenuator of Runx2 in the transcriptional program of osteoblast cytoplasmic differentiation
Stat1 functions as a attenuator of Runx2 in the transcriptional program of osteoblast cytoplasmic differentiation
复制标题
DOI：
10.1101/gad.1119303
复制
发表时间：
2003-08-15
影响因子：
10.5
通讯作者：
Takayanagi, H
中科院分区：
文献类型：
--
作者：
Kim, S;Koga, T;Takayanagi, H
骨重建是维持骨骼系统完整性的核心，其中发育的骨通过成骨细胞骨形成和成骨细胞骨吸收的平衡作用不断更新。在本研究中，我们证明了Stat 1转录因子在骨重建调控中的新功能。在Stat 1缺陷小鼠的骨中，观察到破骨细胞过度生成，推测是由干扰素（IFN）-β对破骨细胞分化的负调控丧失引起的。然而，这些小鼠的骨量意外增加。这种增加是由成骨细胞过度分化引起的，其中Stat 1功能不依赖于IFN信号传导。事实上，Stat 1在细胞质中以其潜伏形式与Runx 2相互作用，从而抑制Runx 2的核定位，Runx 2是成骨细胞分化的必需转录因子。Stat 1的新功能不需要当Stat 1成为转录激活因子时磷酸化的Tyr 701。我们的研究提供了一个独特的例子，其中一个潜在的转录因子减弱了细胞质中另一个转录因子的活性，并揭示了骨重建的一个新的调控机制。
Bone remodeling is central to maintaining the integrity of the skeletal system, wherein the developed bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption. In the present study, we demonstrate a novel function of the Stat1 transcription factor in the regulation of bone remodeling. In the bone of the Stat1-deficient mice, excessive osteoclastogenesis is observed, presumably caused by a loss of negative regulation of osteoclast differentiation by interferon (IFN)-beta. However, the bone mass is unexpectedly increased in these mice. This increase is caused by excessive osteoblast differentiation, wherein Stat1 function is independent of IFN signaling. Actually, Stat1 interacts with Runx2 in its latent form in the cytoplasm, thereby inhibiting the nuclear localization of Runx2, an essential transcription factor for osteoblast differentiation. The new function of Stat1 does not require the Tyr 701 that is phosphorylated when Stat1 becomes a transcriptional activator. Our study provides a unique example in which a latent transcription factor attenuates the activity of another transcription factor in the cytoplasm, and reveals a new regulatory mechanism in bone remodeling.