Mice with increased angiogenesis and osteogenesis due to conditional activation of HIF pathway in osteoblasts are protected from ovariectomy induced bone loss

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• 作者：Qiang Zhao¹ ; Xing Shen¹ ; Wei Zhang ; Guochun Zhu ; Jin Qi ; Lianfu Deng ; ^{deng_lianfu@hotmail.com}
• 关键词：Hypoxia inducible factor (HIF) ; von Hippel&ndash ; Lindau (VHL) ; Ovariectomy ; Angiogenesis ; Osteoblast
• 刊名：Bone
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：50
• 期：3
• 页码：763-770
• 全文大小：1807 K

文摘

Postmenopausal osteoporosis is characterized by a reduction in the numbers of sinusoidal and arterial capillaries in the bone marrow and reduced bone perfusion suggesting a role of vascular component in the pathogenesis of osteoporosis. Previous studies have shown that bone formation and angiogenesis are positively coupled through activation of the hypoxia inducible factor (HIF1¦Á) signaling pathway. Therefore, we hypothesized that mice with increased angiogenesis and osteogenesis due to activation of the HIF signaling pathway in osteoblasts, via osteoblast specific disruption of HIF degrading protein von Hippel-Lindau (VHL) (¦¤Vhl), are protected from ovariectomy induced bone loss. ¦¤Vhl mice and control littermates were ovariectomized or sham operated and four weeks later bone quality was evaluated along with blood vessel formation. Trabecular and cortical bone volume was strikingly increased in ¦¤Vhl mice along with blood vessel formation as compared to control littermates. In control mice, ovariectomy significantly decreased bone mineral density, deteriorated bone microarchitecture, and decreased mechanical strength compared to the sham operated control mice. This was accompanied with a significant decrease in blood vessel volume and expressions of HIF1¦Á, HIF2¦Á, and VEGF proteins at the distal femur in ovariectomized control mice. In contrast, ovariectomy in ¦¤Vhl mice had absolutely no effect on either the blood vessel formation or the bone structural and mechanical quality parameters. These data indicate that activation of HIF signaling pathway in osteoblasts may prevent estrogen deficiency-induced bone loss and decrease in blood vessels in bone marrow.