Li Jiadong, Yin Zhifeng, Huang Biaotong, Xu Ke, Su Jiacan
Institute of Translational Medicine, Shanghai University, Shanghai, China.
School of Medicine, Shanghai University, Shanghai, China.
Front Pharmacol. 2022 Apr 25;13:897539. doi: 10.3389/fphar.2022.897539. eCollection 2022.
Signal transducer and activator of transcription 3 (Stat3) is activated by phosphorylation and translocated to the nucleus to participate in the transcriptional regulation of DNA. Increasing evidences point that aberrant activation or deletion of the Stat3 plays a critical role in a broad range of pathological processes including immune escape, tumorigenesis, and inflammation. In the bone microenvironment, Stat3 acts as a common downstream response protein for multiple cytokines and is engaged in the modulation of cellular proliferation and intercellular interactions. Stat3 has direct impacts on disease progression by regulating mesenchymal stem cells differentiation, osteoclast activation, macrophage polarization, angiogenesis, and cartilage degradation. Here, we describe the theoretical basis and key roles of Stat3 in different bone-related diseases in combination with experiments and animal models. Then, we summarize and categorize the drugs that target Stat3, providing potential therapeutic strategies for their use in bone-related diseases. In conclusion, Stat3 could be a future target for bone-related diseases.
信号转导及转录激活因子3（Stat3）通过磷酸化被激活，并转移至细胞核参与DNA的转录调控。越来越多的证据表明，Stat3的异常激活或缺失在包括免疫逃逸、肿瘤发生和炎症在内的广泛病理过程中起关键作用。在骨微环境中，Stat3作为多种细胞因子的共同下游反应蛋白，参与细胞增殖和细胞间相互作用的调节。Stat3通过调节间充质干细胞分化、破骨细胞激活、巨噬细胞极化、血管生成和软骨降解，对疾病进展产生直接影响。在此，我们结合实验和动物模型描述Stat3在不同骨相关疾病中的理论基础和关键作用。然后，我们对靶向Stat3的药物进行总结和分类，为其在骨相关疾病中的应用提供潜在的治疗策略。总之，Stat3可能成为骨相关疾病未来的治疗靶点。
