[The regulation of hypoxia inducible factor-1alpha on osteoblast function in postmenopausal osteoporosis].
OBJECTIVE
To study the regulation of hypoxia inducible factor-1alpha (HIF-1alpha) on osteoblast function in postmenopausal osteoporosis.


METHODS
From October 2004 to May 2006, Cre-Loxp recombinase was used to create mice which the HIF-1alpha gene in osteoblasts was conditional knock-out, 24 female wild-type (WT) mice and 24 female conditional knock-out (CKO) mice of 3 months old were operated on ovariotomy. At 0,4,8 weeks after operation, bone histomorphometry parameters were measured with computer image analysis in HE stain sections and in tetracycline bone double labeling fluorescence sections; Bone density and the trabecular bone architecture parameters were measured by Micro-CT; The mRNA expression of vascular endothelial growth factors (VEGF), RunX2, OC, ALP were detected with quantitative RT-PCR; The protein expression of VEGF and RunX2 were detected with Western-blotting.


RESULTS
In CKO mice, the trabecular number, volume, thickness, bone density, mineral apposition rate (MAR), the expression of VEGF, RunX2, OC, ALP on mRNA level and the expression of VEGF, RunX2 on protein level decreased significantly compared with WT mice especially in 8 weeks after operation.


CONCLUSIONS
The bone formation ability of osteoblasts in CKO mice was reduced compared with WT mice after ovariotomy. HIF-1alpha can regulate the bone formation ability of osteoblasts in postmenopausal osteoporosis.
Liu
Xiao-dong
XD
Shanghai Institute of Traumatology and Orthopedics, Department of Orthopedics, Shanghai Jiaotong University Affiliated Ruijin Hospital, Shanghai 200025, China.
Deng
Lian-fu
LF
Wang
Jun
J
Qi
Jin
J
Zhou
Qi
Q
Wang
Jin-shen
JS
Wei
Li
L
Zhu
Ya-ping
YP
Clemens
Tl
T
D000818:Animals; D015153:Blotting, Western; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D015663:Osteoporosis, Postmenopausal / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D010052:Ovariectomy; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A