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中华损伤与修复杂志(电子版) ›› 2016, Vol. 11 ›› Issue (02) : 135 -140. doi: 10.3877/cma.j.issn.1673-9450.2016.02.012

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综述

骨转移瘤的溶骨与成骨机制研究进展
雷明星1, 刘耀升1, 刘蜀彬1,()   
  1. 1. 100071 北京,解放军第三〇七医院骨科
  • 收稿日期:2016-02-01 出版日期:2016-04-01
  • 通信作者: 刘蜀彬
  • 基金资助:
    北京市科委首都临床特色课题(z131107002213052)

Research progress on the osteoclastic and osteoblastic mechanisms of bone metastasis

Mingxing Lei1, Yaosheng Liu1, Shubin Liu1,()   

  1. 1. Department of Orthopaedic Surgery, the 307th Hospital of People′s Liberation Army, Beijing 100071, China
  • Received:2016-02-01 Published:2016-04-01
  • Corresponding author: Shubin Liu
  • About author:
    Corresponding author: Liu Shubin, Email:
引用本文:

雷明星, 刘耀升, 刘蜀彬. 骨转移瘤的溶骨与成骨机制研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2016, 11(02): 135-140.

Mingxing Lei, Yaosheng Liu, Shubin Liu. Research progress on the osteoclastic and osteoblastic mechanisms of bone metastasis[J/OL]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2016, 11(02): 135-140.

骨骼是一种动态重塑的组织,终身以骨质溶解和骨质形成的方式进行骨骼动态重塑循环。骨微环境适宜实体肿瘤定植与生长。实体肿瘤骨转移发生率高,骨转移瘤可以导致明显溶骨性和(或)成骨性骨病灶,如乳腺癌主要以溶骨性病灶为典型,前列腺癌主要以成骨性病灶为主。骨转移瘤的骨骼生理以过度溶骨和(或)成骨为中心。溶骨和成骨的主要机制相互区别独立,本质上均为溶骨与成骨的相关因子打破机体正常骨骼重塑动态循环:RANK-RANKL-OPG系统、甲状旁腺激素相关肽和转移生长因子β参与溶骨,Wnts、内皮素1、甲状旁腺激素相关肽和骨形态发生蛋白参与成骨。骨转移瘤的溶骨与成骨效应都属于正反馈性"恶性循环"。本综述在理解正常骨骼生理与骨骼重塑动态循环的基础上重点阐述骨转移瘤的溶骨和成骨生理机制。探索骨转移瘤的溶骨和成骨生理机制可以为研究者研发靶向药物提供契机。

Bone is a dynamic tissue that undergoes bone remodeling throughout life with the types of osteoblasts and osteoclasts. Bone microenvironments facilitate the colonization and growth of solid tumor. The incidence of bone metastasis from solid tumor is high. Bone metastasis can lead to osteoblastic and/or osteoclastic focuses. Breast cancer is characterized by osteoclastic focuses, while osteoblastic focuses are mainly seen in prostate cancer. The bone physiology of bone metastasis lay center on over osteoclasts and/or osteoblasts. Osteoclastic and osteoblastic mechanisms are varies from each other, Osteoclastic and osteoblastic factors break the normal cycle of bone remodeling in nature. RANK-RANKL-OPG system, parathyroid hormone related protein(PTHrP), and transforming growth factor β are involving in osteoclasts; Wnt, endothelin1, PTHrP, and bone morphogenetic proteins participate in osteoblasts. This review focuses on the mechanisms of osteoclasts and osteoblasts on the basement of understanding the normal bone physiology and cycle of bone remodeling. The exploration of osteoblastic and osteoclastic mechanisms related to bone metastasis can provide opportunities for researcher to prevent and treat tumor metastasis to bone.

表1 骨骼动态重塑相关因子
因子 属性 功能
骨质溶解相关因子 ? ?
? RANKL TNF配体家族成员 RANK的配体,促进破骨细胞前体成熟和成熟破骨细胞骨质溶解
? RANK TNF受体家族成员 RANKL的受体,表达于破骨细胞表面,功能同RANKL
? OPG TNF受体家族成员 RANKL的"饵"受体,阻止RANKL结合RANK,对RANKL的功能起到制约作用
? TRAF6 信号分子 RANK下游信号
? SQSTM1 信号分子 TRAF6下游信号
? NF-κB 转录因子 SQSTM1下游信号,结合破骨细胞分化相关基因
? DC-STAMP 跨膜受体 单核破骨细胞前体融合形成多核破骨细胞所必须
? CCN2 细胞因子 调节RANK-RANKL-OPG系统,增强DC-STAMP表达
? PTHrP 蛋白分子 上调RANKL,下调OPG
? CSF1 细胞因子 促造血干细胞分化为破骨细胞前体和巨噬细胞
? c-src蛋白 信号分子 形成破骨细胞褶皱缘
? TCIRG1/CIC7 基因 编码质子泵和氯泵
? 组蛋白酶K 蛋白水解酶 溶解I型胶原
? RGD序列 多肽分子 介导破骨细胞黏附细胞外基质
骨质形成相关因子 ? ?
? Cbfa1/Osx 转录因子 结合成骨细胞基因增强子
? LRP5 Wnt蛋白受体 作用于Cbfa1/Osx下游,促进成骨
? BMP 生长因子 促进成骨细胞增殖和分化
? Wnt家族蛋白 LRP5配体 Wnt/β-catenin信号途径促进骨质形成
? LRP5 Wnt蛋白受体 传递Wnt蛋白信号
? ET-1 ETAR受体 ET-1/β-catenin信号途径促进骨质形成
? PTHrP 蛋白分子 PTHrP的N-末端片段可以模拟ET-1与成骨细胞ETAR结合促进骨质形成
? PSA 肿瘤特异性抗原 调控RANK-RANKL-OPG系统,灭活PTHrP的溶骨效应
? SOST LRP5"饵"配体 骨细胞产生,拮抗Wnt蛋白效应,抑制骨质形成
? DKK-1 LRP5"饵"配体 拮抗Wnt蛋白效应,抑制骨质形成
图1 骨骼重塑动态循环
图2 骨转移瘤病灶影像学表现
图3 骨转移瘤的溶骨机制
图4 骨转移瘤骨质形成机制
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