Cao Jay J, Gregoire Brian R, Gao Hongwei
USDA, Agricultural Research Service, Grand Forks Human Nutrition Research Center, 2420 2nd Ave N, Grand Forks, ND 58202-9034, USA.
Bone. 2009 Jun;44(6):1097-104. doi: 10.1016/j.bone.2009.02.017. Epub 2009 Mar 3.
Body mass has a positive effect on bone health. Whether mass derived from an obesity condition or excessive fat accumulation is beneficial to bone has not been established; neither have the mechanisms by which obesity affects bone metabolism. The aim of this study was to examine the effects of obesity on bone structure and osteoblastic expression of key markers involved in bone formation and resorption in a diet-induced obesity mouse model. Six-wk-old male C57BL/6 mice (n=21) were assigned to two groups and fed either a control (10 kcal% energy as fat) or high-fat diet (HFD, 45 kcal% energy as fat) for 14 weeks. Bone marrow stromal/osteoblastic cells (BMSC) were cultured. Osteoprogenitor activity [alkaline phosphatase (ALP) positive colonies] and mineralization (calcium nodule formation) were determined. Gene expression was measured using quantitative real-time PCR. Bone structure of proximal and midshaft tibia was evaluated by micro-computed tomography. Mice fed the HFD were 31% heavier (P<0.01) than those fed the control diet. There were more ALP positive colony forming units at d 14 and calcium nodules at d 28 of culture by BMSC from HFD mice than from control mice (P<0.01). Receptor activator of NF-kappaB ligand (RANKL) mRNA levels and the ratio of RANKL to osteoprotegerin expression in HFD animals was higher (P<0.01) than in control diet animals. Serum tartrate-resistant acid phosphatase levels were higher in HFD fed mice when compared to control diet fed mice (P<0.05). There were no significant differences in tibial fat-free weight, length, and cortical parameters of midshaft between the two groups. Compared with control mice, tibial trabecular bone volume was reduced, and trabecular separation was increased in HFD mice. Trabecular number was lower (P<0.05) and connectivity density tended to be less (P=0.07) in HFD mice than in control mice. In conclusion, our data indicate that obesity induced by a high-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice.
体重对骨骼健康有积极影响。源自肥胖状况或过多脂肪堆积的体重是否对骨骼有益尚未明确；肥胖影响骨代谢的机制也不清楚。本研究的目的是在饮食诱导的肥胖小鼠模型中，研究肥胖对骨骼结构以及参与骨形成和骨吸收的关键标志物的成骨细胞表达的影响。将6周龄雄性C57BL/6小鼠（n = 21）分为两组，分别给予对照饮食（脂肪提供10%的能量）或高脂饮食（HFD，脂肪提供45%的能量），持续14周。培养骨髓基质/成骨细胞（BMSC）。测定成骨祖细胞活性[碱性磷酸酶（ALP）阳性集落]和矿化（钙结节形成）。使用定量实时PCR测量基因表达。通过显微计算机断层扫描评估胫骨近端和中段的骨骼结构。喂食高脂饮食的小鼠比喂食对照饮食的小鼠重31%（P<0.01）。与对照小鼠相比，高脂饮食小鼠的BMSC在培养第14天时形成的ALP阳性集落形成单位更多，在第28天时形成的钙结节更多（P<0.01）。高脂饮食动物中核因子κB受体活化因子配体（RANKL）mRNA水平以及RANKL与骨保护素表达的比值高于对照饮食动物（P<0.01）。与喂食对照饮食的小鼠相比，喂食高脂饮食的小鼠血清抗酒石酸酸性磷酸酶水平更高（P<0.05）。两组之间胫骨无脂重量、长度和中段皮质参数无显著差异。与对照小鼠相比，高脂饮食小鼠的胫骨小梁骨体积减少，小梁间距增加。高脂饮食小鼠的小梁数量较低（P<0.05），连接密度趋于更低（P = 0.07）。总之，我们的数据表明，高脂饮食诱导的肥胖会降低小鼠胫骨的松质骨量，但对皮质骨量没有影响。
