巨噬细胞源性破骨细胞在血管钙化中的作用  

Role of Macrophage-derived Osteoclasts in Vascular Calcification

作　　者：王中群[1] 张莉莉 赵云云 李丽华[2,3] 袁伟 WANG Zhong-Qun;ZHANG Li-Li;ZHAO Yun-Yun;LI Li-Hua;YUAN Wei(Department of Cardiology,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China;Department of Pathology,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China;Guangxi Key Laboratory of Diabetic Systems Medicine,The Second Affiliated Hospital of Guilin Medical University,Guilin 541100,China)

机构地区：[1]江苏大学附属医院心内科,镇江212001 [2]江苏大学附属医院病理科,镇江212001 [3]桂林医学院第二附属医院糖尿病系统医学广西重点实验室,桂林541100

出　　处：《生物化学与生物物理进展》2022年第12期2355-2363,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(82070455);江苏省卫健委项目(M2020016);广西糖尿病系统医学重点实验室开放计划(GKLCDSM-20210101-02);江苏省医学创新团队项目(CXTDA2017010)资助。

摘　　要：血管钙化是一种细胞介导的主动生物学过程,类似于骨重塑,在急慢性心脑血管事件的发生与演进过程中发挥了重要的推动作用。近年来有关血管钙化的机制与防治研究逐渐受到广大学者的关注,但遗憾的是,精准的分子与细胞靶向治疗尤其是能在临床推广应用的成果却罕有出现。新近的研究显示,糖尿病动脉粥样硬化斑块中存在成骨细胞表型和功能失调的破骨细胞表型,成骨细胞与破骨细胞调控的失衡可能是动脉粥样硬化斑块内钙化形成的关键环节。已知由巨噬细胞分化而来的破骨细胞是机体内唯一有骨吸收特性的细胞,具备促钙化消退的潜能。因此,探索促斑块内巨噬细胞源性破骨细胞骨吸收活性的研究是一个有望为钙化防治带来新突破的方向。然而,目前关于破骨细胞在血管钙化中的作用和相关调控机制仍存在争议。基于该领域的研究进展和本课题组的实验结果,本文凝练出了羧甲基赖氨酸(CML)通过STAT3调控NFATc1-GNPTAB信号介导斑块内巨噬细胞破骨化吸收障碍的假说,并从血管钙化的概念与机制、破骨细胞与血管钙化间的关系、血管钙化中破骨细胞的调控机制以及破骨细胞作为血管钙化治疗靶点4个方面进行简要阐述,希望为后续血管钙化的精准防治提供新的切入点。Vascular calcification is a cell-mediated active biological process,similar to bone remodeling,and plays an important role in the occurrence and evolution of acute and chronic cardiovascular and cerebrovascular events.In recent years,the research on the mechanism and prevention of vascular calcification has gradually attracted the attention of scholars,but unfortunately,precise molecular and cellular targeted therapy for clinical application is rare.Previous studies have shown the presence of the osteoblast phenotype and dysfunctional osteoclasts in atherosclerotic plaques of diabetes.The imbalance of osteoblasts and osteoclasts may be the key step in calcification development in atherosclerotic plaques.It is known that macrophage-derived osteoclasts are the only cells with bone resorption activity and have the potential to reverse calcification.Therefore,exploring the bone resorption activity of macrophage-derived osteoclasts in the plaque is a promising direction to bring new breakthroughs in the prevention and treatment of calcification.However,the role and related regulatory mechanism of osteoclasts in vascular calcification may still be controversial nowadays.Based on the research progress that has been made in this field and the experimental results of our research group,this article puts forward the hypothesis that Nε-carboxymethyl-lysine(CML)mediates NFATc1-GNPTAB through STAT3 to regulate the osteoclastic absorption barrier of macrophages in plaques and provides a brief review of the following 4 aspects:concept and mechanism of vascular calcification,relationship between osteoclasts and vascular calcification,mechanism of osteoclasts in vascular calcification,and osteoclasts as a therapeutic target for vascular calcification.It is hoped that this paper will offer a new entry point for the precise prevention and treatment of vascular calcification.

关 键 词：羧甲基赖氨酸 活化T细胞核因子C1 破骨细胞 血管钙化 

分 类 号：R543.1[医药卫生—心血管疾病]