In vivo and in vitro characteristic of HIF-1α and relative genes in ischemic femoral head necrosis.
BACKGROUND
Legg-Calvé-Perthes Disease (Perthes' disease) is a childhood hip disorder initiated by ischemic necrosis of the growing femoral head. So far, the etiology and pathogenesis of Perthes' disease is poorly understood.


METHODS
Avascular osteonecrosis rat model was established to mimic the pathophysiological changes of femoral head necrosis. The chondrocytes of newborn Sprague-Dawley rats were isolated and cultured in hypoxic and normoxic condition. The expression characteristic of the hypoxia-inducible factor-1 alpha (HIF-1α) was evaluated both in vivo and in vitro models. Vascular endothelial growth factor (VEGF) and apoptotic genes in chondrocytes treated with normoxia and hypoxia were also studied.


RESULTS
HIF-1α expression increased greatly after ischemic operation and kept at relative high level in the arthromeningitis stage and declined in the stages of osteonecrosis and reconstruction. The HIF-1α mRNA levels of chondrocytes incubated at hypoxia were significantly higher than the cells treated with normoxia at 24 and 72 hours. Hypoxia inhibited VEGF expression; chondrocytes could oppose this inhibition manifested by the increasing of VEGF mRNA level after 72 hours hypoxia. The expression of apoptotic genes, Casp3, Casp8 and Casp9, elevated in chondrocytes after hypoxia with time differences.


CONCLUSIONS
Hypoxia might be an etiological factor for femoral head necrosis, HIF-1α, VEGF as well as apoptotic genes participated the pathophysiological process of ischemic osteonecrosis.
Department of Pediatric Orthopaedics, Children's Hospital of Fudan University 399 Wanyuan Road, Minhang District, Shanghai 201102, China.
Wanglin
W
Zhang
Department of Pediatric Orthopaedics, Children's Hospital of Fudan University 399 Wanyuan Road, Minhang District, Shanghai 201102, China.
Zhe
Z
Yuan
Department of Pediatric Orthopaedics, Children's Hospital of Fudan University 399 Wanyuan Road, Minhang District, Shanghai 201102, China.
Xinhong
X
Pei
Department of Pediatric Orthopaedics, Children's Hospital of Fudan University 399 Wanyuan Road, Minhang District, Shanghai 201102, China.
Ruixue
R
Ma
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005270:Femur Head / Q000378:metabolism* / Q000473:pathology; D005271:Femur Head Necrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020169:Caspases
Legg-Calvé-Perthes Disease; apoptotic genes; hypoxia-inducible factor-1 alpha (HIF-1α); ischemic osteonecrosis; vascular endothelial growth factor (VEGF)