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学科主题: 临床医学
题名:
Smad3 is the key to transforming growth factor-beta 1-induced osteoclast differentiation in giant cell tumor of bone
作者: Lou, Zhiyuan; Yang, Yi; Ren, Tingting; Tang, Shun; Peng, Xianbo; Lu, Qunshan; Sun, Yifeng; Guo, Wei
关键词: Giant cell tumor of bone ; Osteoclast differentiation ; Receptor activator of nuclear factor kappa B ligand ; Osteoprotegerin ; Immunohistochemistry ; Transforming growth factor-beta 1
刊名: MEDICAL ONCOLOGY
发表日期: 2013-09-01
DOI: 10.1007/s12032-013-0606-8
卷: 30, 期:3
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: FACTOR-BETA ; OSTEOPROTEGERIN LIGAND ; POSSIBLE INVOLVEMENT ; RECEPTOR ACTIVATOR ; HUMAN OSTEOBLASTS ; GENE-EXPRESSION ; STROMAL CELL ; TGF-BETA ; KAPPA-B ; RANKL
英文摘要:

Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm of bone. However, molecular mechanisms underlying osteolysis in GCT have not been deeply understood. The aim of this study was to investigate one of the possible mechanisms underlying the up-regulation of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) expression. First, we performed an immunohistochemical study on transforming growth factor-beta 1 (TGF-beta 1) expression in 83 cases with GCT and found that increased TGF-beta 1 staining was significantly correlated with Campanacci stages(Spearman′s correlation = 0.335, p = 0.002). Next, we investigated the mechanism of the effect of TGF-beta 1 on osteolysis of GCT and examined the effects of TGF-beta 1 plus or minus specific inhibitor of Smad3 (SIS3) on the expression of RANKL/OPG ratio at the mRNA and protein levels in two primary GCT cell lines. The results clearly indicated that TGF-beta 1 is capable of significantly increasing RANKL/OPG ratio (p(GCT1) = 0.000, p(GCT2) = 0.000) and that SIS3 is capable of reversing the ratio, suggesting that Smad3 is the key to TGF-beta 1-induced increased the ratio. In the co-culture system, we found that SIS3 reversed the effects of TGF-beta 1-induced osteoclast formation in the co-culture system (p(GCT1) = 0.000, p(GCT2) = 0.000). Our findings indicate that TGF-beta 1 plays an important role in the osteolysis of GCT via Smad3.

语种: 英语
所属项目编号: 81172543 ; 81001193
项目资助者: National Natural Sciences Foundation of China
WOS记录号: WOS:000323662900087
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67261
Appears in Collections:北京大学第二临床医学院_骨肿瘤科_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Lou, Zhiyuan,Yang, Yi,Ren, Tingting,et al. Smad3 is the key to transforming growth factor-beta 1-induced osteoclast differentiation in giant cell tumor of bone[J]. MEDICAL ONCOLOGY,2013,30(3).
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