Chinese Journal of Tissue Engineering Research ›› 2015, Vol. 19 ›› Issue (51): 8201-8207.doi: 10.3969/j.issn.2095-4344.2015.51.001

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Hypoxia inducible factor-1 alpha and apoptosis of osteocytes in steroid-induced avascular necrosis of the femoral head 

Zhao Zhen-qun1, Zhang Zhi-feng2, Liu Wan-lin1, Bai Rui1, Wang Wen-xuan3, Sun Liang1   

  1. the Second Affiliated Hospital of Inner Mongolia Medical University, 1Department of Pediatric Orthopedics, 2Department of Joint Surgery, 3Department of Hand and Foot Surgery, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China
  • Received:2015-11-04 Online:2015-12-10 Published:2015-12-10
  • Contact: Bai Rui, M.D., Associate chief physician, Department of Pediatric Orthopedics, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China
  • About author:Zhao Zhen-qun, Master, Attending physician, Department of Pediatric Orthopedics, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China Zhang Zhi-feng, Master, Attending physician, Department of Joint Surgery, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China Zhao Zhen-qun and Zhang Zhi-feng contributed equally to this work.
  • Supported by:

    the Natural Science Foundation of Inner Mongolia Autonomous Region, No. 2015MS08121; the Scientific Research Program in Universities of Inner Mongolia Autonomous Region, No. NJZY14138; a grant from the Second Affiliated Hospital of Inner Mongolia Autonomous Region, No. 2013YJJ17

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Abstract:

BACKGROUND: Although the pathogenesis of steroid-induced avascular necrosis of the femoral head is unknown, ischemia/hypoxia is the fundamental reason. Under hypoxic conditions, hypoxia-inducible factor-1α is involved in various signal transduction pathways. Preliminary studies have found that osteocyte apoptosis is associated with steroid-induced avascular necrosis of the femoral head.
OBJECTIVE: To investigate the relationship between hypoxia inducible factor-1α and apoptosis in steroid-induced avascular necrosis of the femoral head.
METHODS: Twenty New Zealand white rabbits, 5 months old, were randomly divided into control group and experimental group, 10 rabbits in each group. Animal models of avascular necrosis of the femoral head were 
made in the experimental group using steroid and endotoxin. Four weeks after the final administration, all animals were sacrificed to take the bilateral femoral heads that were observed morphologically and ultrastructurally under electron microscope. Number of vacant lacunae was calculated in each group. Immunohistochemical technique and TUNEL methods were used to detect hypoxia inducible factor-1α and osteocyte apoptosis, respectively.
RESULTS AND CONCLUSION: Lacuna vacancy rate of the experimental group was higher than that of the control group (P < 0.01); the osteocyte apoptosis rate of the experimental group was higher than that of the control group     (P < 0.01). In the experimental group, the apoptosis rate was negatively correlated with the expression of hypoxia inducible factor-1α (r=-0.675), but positively correlated with the lacuna vacancy rate (r=0.793). These findings indicate that in the early stage of steroid-induced avascular necrosis, low expression of hypoxia-inducible factor-1α is related with apoptosis of osteocytes, and they are both involved in the pathological process of femoral head necrosis. Apoptosis is the death way of osteocytes. 

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