ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells
ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells
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DOI：
10.1359/jbmr.070330
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发表时间：
2007-07-01
影响因子：
6.2
通讯作者：
Nakamura, Toshitaka
中科院分区：
文献类型：
--
作者：
Hirasawa, Hideyuki;Tanaka, Shinya;Nakamura, Toshitaka
高脂饮食apoE（-/-）小鼠胫骨成骨细胞凋亡增加，骨形成减少。骨髓贴壁细胞p53 mRNA表达增加。LDL或氧化LDL增加apoE（-/-）小鼠颅骨细胞的凋亡。p53介导的细胞凋亡的增加显然与apoE（-/-）mouse.Introduction中高脂饮食诱导的骨质减少有关：高脂负荷和载脂蛋白E（apoE）基因对骨骼的影响尚未阐明。我们假设，载脂蛋白E基因缺陷（apoE（-/-））调制的影响，高脂负荷对bones.Materials和Methods：我们评估了这一假设，使用野生型（WT）和apoE（-/-）小鼠喂养标准（WTS和ApoES组）或高脂饮食（WTHf和ApoEHf组）。检测血脂水平和骨化学指标。使用mu CT和显微镜进行股骨的组织形态计量学。取股骨骨髓贴壁细胞进行成纤维细胞集落形成单位（CFU）测定和mRNA表达分析。计数胫骨凋亡细胞。结果：ApoEHf组大鼠股骨皮质骨体积、骨小梁和皮质内骨形成减少，尿脱氧吡啶啉增加。随后的分析显示，ApoES组胫骨中凋亡细胞的数量增加，ApoEHf组更是如此。ApoEHf组碱性磷酸酶阳性CFU-f占总CFU-f的比例降低。apoE（-/-）小鼠贴壁细胞p53 mRNA表达增加，且与血清LDL呈显著正相关。成骨细胞TUNEL荧光染色显示apoE（-/-）小鼠成骨细胞凋亡增加。apoE（-/-）小鼠中凋亡细胞的数量随着加入100 μ g/ml LDL或氧化LDL而增加。暴露于100 μ g/ml LDL或氧化LDL的apoE（-/-）细胞中的p53蛋白表达increased.Conclusions：我们的结论是，apoE基因缺陷增强通过刺激p53介导的成骨细胞凋亡的高脂饮食诱导的骨形成的减少。
Osteoblast apoptosis increased in the tibias of apoE(-/-) mice fed with a high-fat diet, decreasing bone formation. The expression of p53 mRNA in marrow adherent cells increased. LDL or oxidized LDL increased apoptosis in the calvarial cells of apoE(-/-) mice. The increase in p53-mediated apoptosis is apparently related to a high-fat diet-induced osteopenia in apoE(-/-) mice.Introduction: The effects of high-fat loading and the apolipoprotein E (apoE) gene on bones have not been elucidated. We hypothesized that apoE gene deficiency (apoE(-/-)) modulates the effects of high-fat loading on bones.Materials and Methods: We assessed this hypothesis using wildtype (WT) and apoE(-/-) mice fed a standard (WTS and ApoES groups) or a high-fat diet (WTHf and ApoEHf groups). The concentration of serum lipid levels and bone chemical markers were measured. Histomorphometry of the femurs was performed using mu CT and a microscope. Bone marrow adherent cells from the femurs were used for colony-forming unit (CFU)-fibroblastic (CFU-f) assay and mRNA expressions analysis. The apoptotic cells in the tibias were counted. TUNEL fluorescein assay and Western analysis were performed in cultures of calvarial cells by the addition of low-density lipoprotein (LDL) or oxidized LDL.Results: In the ApoEHf group, the values of cortical bone volume and trabecular and endocortical bone formation of the femurs decreased, and urinary deoxypyridinoline increased. Subsequent analysis revealed that the number of apoptotic cells in the tibias of the ApoES group increased, and more so in the ApoEHf group. The ratio of alkaline phosphatase-positive CFU-f to total CFU-f was decreased in the ApoEHf group. p53 mRNA expression in adherent cells of the apoE(-/-) mice increased and had a significantly strong positive correlation with serum LDL. TUNEL fluorescein assay of osteoblastic cells revealed an increase of apoptotic cells in the apoE(-/-) mice. The number of apoptotic cells in the apoE(-/-) mice increased with the addition of 100 mu g/ml LDL or oxidized LDL. The p53 protein expression in apoE(-/-) cells exposed to 100 mu g/ml LDL or oxidized LDL increased.Conclusions: We concluded that apoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells.