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Adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 inhibits the formation of heterotopic ossification in animal model
Lin, Lin; Chen, Lianxu; Wei, Xuelei; Fu, Xin; Zhang, Jiying; Ma, Kangtao; Zhou, Chunyan; Yu, Changlong
关键词Sirna Runx2/cbfa1 Osteoblast Gene Therapy Heterotopic Ossification Adenovirus
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2006-10-20
DOI10.1016/j.bbrc.2006.08.089
349期:2页:564-572
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]TOTAL HIP-ARTHROPLASTY ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; TRAUMATIC BRAIN-INJURY ; MESENCHYMAL STEM-CELLS ; ECTOPIC BONE-FORMATION ; OSTEOBLAST DIFFERENTIATION ; RNA INTERFERENCE ; IN-VITRO ; CLEIDOCRANIAL DYSPLASIA ; ENHANCED OSTEOGENESIS
英文摘要

The heterotopic ossification of muscles, tendons, and ligaments is a common problem faced by orthopaedic surgeons. Runx2/Cbfa1 plays an essential role during the osteoblast differentiation and is considered as a molecular switch in osteoblast biology. RNA interference technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. In this study, we investigated the effect of Runx2/Cbfa1-specific siRNA on osteoblast differentiation and mineralization in osteoblastic cells, and then constructed adenovirus containing siRNA against Runx2/Cbfa1 (Ad-Runx2-siRNA) to inhibit the formation of heterotopic ossification induced by BMP4, dernineralized bone matrix, and trauma in animal model. Our results showed that the Runx2/Cbfa1-specific siRNA could inhibit the expression of Runx2/Cbfa1 at the level of mRNA and protein. Analysis of the expression of osteoblast maturation genes including type I collagen, osteopontin, bone sialoprotein, and osteocalcin, alkaline phosphatase activity, and matrix mineralization (von kossa) revealed that osteoblast differentiation was inhibited in cultured primary mouse osteoblasts transduced with Ad-Runx2-siRNA. Furthermore, adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 could inhibit the formation of heterotopic ossification induced by BMP4, dernineralized bone matrix, and trauma in animal model. It is likely that the inhibition of Runx2/Cbfa1 by RNAi could be developed as a powerful approach to prevent or treat heterotopic ossification. (c) 2006 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000240791800016
引用统计
被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56527
专题北京大学第三临床医学院_运动医学研究所
作者单位1.Peking Univ Third Hosp, Inst Sports Med, Beijing 100083, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
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Lin, Lin,Chen, Lianxu,Wei, Xuelei,et al. Adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 inhibits the formation of heterotopic ossification in animal model[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2006,349(2):564-572.
APA Lin, Lin.,Chen, Lianxu.,Wei, Xuelei.,Fu, Xin.,Zhang, Jiying.,...&Yu, Changlong.(2006).Adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 inhibits the formation of heterotopic ossification in animal model.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,349(2),564-572.
MLA Lin, Lin,et al."Adenovirus-mediated transfer of siRNA against Runx2/Cbfa1 inhibits the formation of heterotopic ossification in animal model".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 349.2(2006):564-572.
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