OBJECTIVETo study the regulation of hypoxia inducible factor-1alpha (HIF-1alpha) on osteoblast function in postmenopausal osteoporosis.

METHODSFrom 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.

RESULTSIn 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.

CONCLUSIONSThe 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.

Animals ; Blotting, Western ; Core Binding Factor Alpha 1 Subunit ; genetics ; metabolism ; Disease Models, Animal ; Female ; Femur ; metabolism ; pathology ; physiopathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoblasts ; metabolism ; physiology ; Osteoporosis, Postmenopausal ; genetics ; metabolism ; physiopathology ; Ovariectomy ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism