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学科主题: 临床医学
题名:
Non-virus-mediated transfer of siRNAs against Runx2 and Smad4 inhibit heterotopic ossification in rats
作者: Xue, T.1; Mao, Z.2; Lin, L.1; Hou, Y.1; Wei, X.3; Fu, X.1; Zhang, J.1; Yu, C.1
关键词: siRNA ; Runx2 ; Smad4 ; non-virus ; heterotopic ossification
刊名: GENE THERAPY
发表日期: 2010-03-01
DOI: 10.1038/gt.2009.154
卷: 17, 期:3, 页:370-379
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: TOTAL HIP-ARTHROPLASTY ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; BONE MORPHOGENETIC PROTEIN-2 ; TRAUMATIC BRAIN-INJURY ; OSTEOBLAST DIFFERENTIATION ; CLEIDOCRANIAL DYSPLASIA ; ECTOPIC OSSIFICATION ; ENHANCED OSTEOGENESIS ; GENE-EXPRESSION ; RISK-FACTORS
英文摘要:

Heterotopic ossification of muscles, tendons and ligaments are a common problem affecting patient with trauma or received elective surgery. But the existing preventive or therapeutic methods all have disadvantages. Runt-related protein 2 (Runx2) and Smad4 are two regulators that have important roles in the differentiation of osteoblast. In this study, we attempted to examine the effect of Runx2 and Smad4 on the development of heterotopic ossification in vitro. We constructed non-virus-containing small interference RNAs (siRNAs) against Runx2 and Smad4 and tested it with reverse transcriptase-PCR and western blot. We then analyzed the independent effect of Runx2- and Smad4-specific siRNAs and their cooperative effect on the formation of heterotopic ossification induced by trauma in rats. The effects were measured with computed tomography scanning, hematoxylin and eosin staining and immunohistochemistry. We found that the Runx2 and Smad4-specific siRNAs inhibited the expression of Runx2 and Smad4 at the level of messenger RNA and protein. Runx2 and Smad4 independently inhibited the formation of heterotopic ossification. Moreover, their co-expression significantly enhanced the inhibition of heterotopic ossification compared with the independent effect. We suggest that gene therapy to inhibit Runx2 and Smad4 by RNAi could be a powerful approach to prevent or treat heterotopic ossification. Gene Therapy (2010) 17, 370-379; doi:10.1038/gt.2009.154; published online 26 November 2009

语种: 英语
所属项目编号: ZR09-1-01
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000275392600008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53477
Appears in Collections:北京大学第三临床医学院_运动医学研究所_期刊论文

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作者单位: 1.Tianjin Hosp, Dept Orthoped Surg, Tianjin, Peoples R China
2.Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China

Recommended Citation:
Xue, T.,Mao, Z.,Lin, L.,et al. Non-virus-mediated transfer of siRNAs against Runx2 and Smad4 inhibit heterotopic ossification in rats[J]. GENE THERAPY,2010,17(3):370-379.
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