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学科主题: 临床医学
题名:
Synergistic Inhibition of Endochondral Bone Formation by Silencing Hif1 alpha and Runx2 in Trauma-induced Heterotopic Ossification
作者: Lin, Lin1; Shen, Qi2; Leng, Huijie3; Duan, Xiaoning1; Fu, Xin1; Yu, Changlong1
刊名: MOLECULAR THERAPY
发表日期: 2011-08-01
DOI: 10.1038/mt.2011.101
卷: 19, 期:8, 页:1426-1432
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: HYPOXIA-INDUCIBLE FACTOR ; MESENCHYMAL STEM-CELLS ; OSTEOBLAST DIFFERENTIATION ; SKELETAL DEVELOPMENT ; MEDIATED TRANSFER ; IN-VITRO ; EXPRESSION ; CARTILAGE ; CBFA1 ; SKELETOGENESIS
英文摘要:

Angiogenesis and osteogenesis are tightly coupled during bone development. We studied the effect of inhibition of Hif1 alpha and Runt-related protein 2 (Runx2) on the formation of heterotopic ossification (HO). We constructed lentivirus vectors expressing Hif1 alpha small interfering RNA (siRNA) and Runx2 siRNA. The inhibition of Hif1 alpha function impaired osteoblast proliferation while osteoblasts differentiated normally. Osteoblasts lacking Runx2 proliferated normally while the differentiation was impaired. The osteoblast differentiation was significantly inhibited by co-Runx2 and Hif1 alpha siRNA treatment. The formation of HO by inhibiting Runx2 and Hif1 alpha in an animal model induced by Achilles tenotomy was investigated. The results showed that lacking of Runx2 and Hif1 alpha could inhibit HO formation. Inhibition of Hif1 alpha prevented HO formation only at the initial step and inhibition of Runx2 worked both at the initial step and after chondrogenesis. Angiogenesis and the expressions of osteogenic genes were downregulated in the Hif1 alpha siRNA group. We found synergistic inhibition of endochondral bone formation by silencing Hif1 alpha and Runx2. Our study provided new insight into the roles of Hif1 alpha and Runx2 during the processes of endochondral bone formation, and had important implications for the new therapeutic methods to inhibit HO or to enhance bone formation.

语种: 英语
所属项目编号: 2008B04
项目资助者: Beijing NOVA ; Beijing Municipal Science and Technology Commission ; Doctoral Program Foundation of Institutions of Higher Education of China
WOS记录号: WOS:000293378500006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58028
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.Peking Univ, Hosp 1, Inst Urol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 3, Dept Orthoped, Beijing 100191, Peoples R China

Recommended Citation:
Lin, Lin,Shen, Qi,Leng, Huijie,et al. Synergistic Inhibition of Endochondral Bone Formation by Silencing Hif1 alpha and Runx2 in Trauma-induced Heterotopic Ossification[J]. MOLECULAR THERAPY,2011,19(8):1426-1432.
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