Research progress on the osteoclastic and osteoblastic mechanisms of bone metastasis

doi:10.3877/cma.j.issn.1673-9450.2016.02.012

Abstract

Abstract:

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.

Key words: Skeleton, Bone neoplasms, Neoplasm metastasis, Osteoclasts, Osteoblasts

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

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References 38

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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

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

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