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目的探讨在绝经后骨质疏松的发生、发展过程中,低氧诱导因子-lα(HIF-1α)对于成骨细胞功能的调控作用。方法 2004年10月至2006年5月,应用 Cre-Loxp 重组酶技术,建立成骨细胞条件性敲除 HIF-1α小鼠,取3个月龄雌性野生型和敲除型小鼠各24只行卵巢切除术,术后0、4、8周取材行 HE 染色、四环素荧光双标记、Micro-CT、RT-PCR、Western-blotting 检测。结果与野生型小鼠相比,敲除型小鼠骨小梁的数目、体积、厚度,骨密度,骨矿沉积速度,血管内皮生长因子(VEGF)、RunX2、ALP、OC 基因在 mRNA 水平的表达,VEGF、RunX2在蛋白水平的表达均明显降低,尤其以术后8周最为明显。结论在绝经后骨质疏松的发生、发展过程中,成骨细胞条件性敲除 HIF-1α后成骨功能降低,HIF-1α能够调控成骨细胞的成骨功能。
Objective To investigate the regulatory effect of hypoxia inducible factor-1α (HIF-1α) on the function of osteoblasts in the development of postmenopausal osteoporosis. Methods From Oct. 2004 to May 2006, Cre-Loxp recombinant enzyme technology was used to establish osteoblast conditional knockout HIF-1α mice. Twenty-four female wild-type and knock-out mice Ovaryctomy was performed at 0, 4 and 8 weeks after operation. HE staining, double-labeling with tetracycline fluorescence, Micro-CT, RT-PCR and Western-blotting were performed. Results Compared with wild-type mice, the number of trabecular bone, volume, thickness, bone mineral density, bone mineral deposition rate, VEGF, RunX2, ALP, OC gene mRNA level The expression of VEGF, RunX2 at the protein level were significantly lower, especially at 8 weeks after the most obvious. Conclusions In the process of postmenopausal osteoporosis, osteoblasts knocked down HIF-1α conditionally and osteoblast function decreased. HIF-1α can regulate the osteoblastic function of osteoblasts.