信号转导与转录活化因子3在骨稳态和机械力介导的骨改建中的作用机制研究进展
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1.上海交通大学医学院·口腔医学院;2.上海交通大学医学院附属第九人民医院,口腔颅颌面科

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The role of signal transducer and activator of transcription 3 in bone homeostasis and load-driven bone remodeling
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    摘要:

    骨稳态是骨的形成与吸收维持相对平衡的过程。信号转导和转录活化因子3(signal transducer and activator of transcription 3, STAT3)参与多条细胞内外的信号转导通路,与骨稳态息息相关。已有研究证明,STAT3参与由众多因素调控的成骨细胞分化过程;也可通过调控破骨细胞的募集、分化和活性等维持骨稳态;还影响骨稳态中成骨-破骨细胞的交互通讯。STAT3突变的患者则表现出多种遗传性骨代谢疾病。此外,STAT3在机械应力介导的骨改建中也起重要作用。研究表明,机械力刺激通过上调或激活STAT3促进成骨分化和骨生成,进而调控骨改建。现综述STAT3在维持骨稳态中的作用以及可能的作用机制,并探讨骨改建中机械力刺激与STAT3的联系,为将STAT3作为靶点应用于骨骼疾病治疗提供研究思路。

    Abstract:

    Bone homeostasis is a relative balance between bone formation and resorption. Signal transducer and activator of transcription 3 (STAT3), which is closely related to bone homeostasis, takes part in multiple intracellular and extracellular signal pathways. STAT3 participates in the process of osteoblast differentiation regulated by several factors. It also plays a role in the maintenance of bone homeostasis by regulating the recruitment, differentiation and activation of osteoclasts. In addition, STAT3 is involved in the interaction between osteoblasts and osteoclasts. Patients with STAT3 mutations can have several inherited bone metabolism diseases. Furthermore, STAT3 has a critical role in load-driven bone remodeling. Mechanical stimulation promotes osteoblast differentiation and bone formation through activating or enhancing STAT3 expression during bone remodeling process. Our review summarizes the participation of STAT3 in maintaining bone homeostasis together with its possible mechanisms and discusses the connection between STAT3 and mechanical stimulation in bone remodeling. It may provide a potential pharmacological target for the treatment of bone diseases.

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历史
  • 收稿日期:2020-09-12
  • 最后修改日期:2020-11-15
  • 录用日期:2020-11-17
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