上海交通大学学报（医学版）

›› 2009, Vol. 29 ›› Issue (11): 1305-.

• 论著（基础研究） • 上一篇    下一篇

低氧诱导因子-1α和VHL对小鼠软骨内成骨过程的调控机制

邵 进, 邓廉夫, 齐 进, 周 琦, 王 君, 魏 立, 王晋申, 钱念东   

  1. 上海交通大学 医学院瑞金医院 骨科 上海市伤骨科研究所, 上海 200025
  • 出版日期:2009-11-25 发布日期:2009-11-24
  • 通讯作者: 邓廉夫, 电子信箱: lfd@msn.com。
  • 作者简介:邵 进（1977—）, 男, 博士生；电子信箱: shaojin_1977@126.com。
  • 基金资助:

    国家自然科学基金（30672145）；上海市科委2006“登山计划”（06DZ22020）；上海市科委2007“创新行动”（07DZ22008）

Role of hypoxia inducible factor-1alpha and VHL in murine endochondral ossification

SHAO Jin, DENG Lian-fu, QI Jin, ZHOU Qi, WANG Jun, WEI Li, WANG Jin-shen, QIAN Nian-dong   

  1. Department of Orthopaedics, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2009-11-25 Published:2009-11-24
  • Supported by:

    National Natural Science Foundation of China, 30672145; Shanghai Science and Technology Committee Foundation, 06DZ22020, 07DZ22008

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摘要：

目的 研究低氧诱导因子1α （HIF-1α）和von Hippel-Lindau （VHL）在成骨细胞水平对小鼠软骨内成骨过程的调控机制。方法 以HIF-1α或VHL基因条件性敲除小鼠为实验对象，分别于4、8、12周龄时，采用组织化学染色观察、显微CT扫描、骨小梁面积测量、钙元素含量检测、四环素荧光双标记观察、Real-time PCR及Western blotting等方法，观察和比较基因敲除小鼠与野生型小鼠（对照组）软骨内成骨过程的差异。结果 与野生型对照小鼠比较，HIF-1α基因敲除组小鼠在软骨内成骨过程中血管内皮生长因子（VEGF）表达减少，新骨形成速度减慢，钙元素含量和骨小梁面积减少（P<0.05）；而VHL基因敲除组小鼠在软骨内成骨过程中VEGF表达增加，新骨形成速度加快，钙元素含量和骨小梁面积增加（P<0.001）。结论 在小鼠软骨内化骨过程中，VHL/HIF-1α信号通路对VEGF表达具有调控作用，通过调节血管形成，最终影响骨量形成。

关键词: 低氧诱导因子-1α, von Hippel-Lindau, 软骨内成骨

Abstract:

Objective To investigate the role of hypoxia inducible factor-1α (HIF-1α) and von Hippel-Lindau (VHL) in murine endochondral ossification. Methods The knockout of HIF-1α or VHL gene in murine osteoblasts was accomplished by conditional knockout technique at 4th, 8th and 12th week, and the differences between wild-type group and knock-out group in endochondral ossification were detected by HE staining, micro-CT scanning, trabecular bone area measurement, calcium content measurement, tetracycline fluorescence labeling, Real-time PCR and Western blotting. Results After knockout of HIF-1α gene in osteoblasts, the expression of vascular endothelial growth factor(VEGF) reduced, the rate of new bone formation stepped down, the content of calcium became less, and the trabecular bone volume decreased （P<0.05）. After knockout of VHL gene in osteoblasts, the expression of VEGF increased, the rate of new bone formation stepped up, the content of calcium became more, and the trabecular bone volume was promoted （P<0.001）. Conclusion During murine endochondral ossification, VHL/HIF-1α signal pathway promotes angiogenesis through the stimulation of VEGF expression，which subsequently accelerates osteogenesis.

Key words: hypoxia inducible factor-1α, von Hippel-Lindau, endochondral ossification