Osteoclastogenesis by Bone Marrow-Derived Macrophages Is Enhanced in Obese Mice

Osteoclastogenesis by Bone Marrow-Derived Macrophages Is Enhanced in Obese Mice
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DOI:
10.3945/jn.108.100032
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发表时间:
2009-03-01
影响因子:
4.2
通讯作者:
Choi, Hye-Seon
Choi, Hye-Seon
中科院分区:
医学2区
文献类型:
--
作者:
Kyung, Tae-Wook;Lee, Ji-Eun;Choi, Hye-Seon

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肥胖诱导低级别的全身性慢性炎症性疾病,巨噬细胞对此负责。我们假设肥胖通过作用于骨髓源性巨噬细胞(BMM)影响破骨细胞生成。雄性小鼠分别饲喂高脂饲料(45%的能量)或标准饲料(10%的能量)13周。我们发现肥胖小鼠股骨的密度明显低于瘦小鼠股骨的密度。破骨细胞生成在肥胖小鼠的BMM中增强。在核因子-κ B配体受体激活剂刺激下,肥胖小鼠BMM产生的白细胞介素(IL)-10水平低于瘦小鼠。中和肥胖小鼠BMM中的IL-10在增加破骨细胞(OC)形成方面不如瘦小鼠有效。外源性IL-10对肥胖小鼠BMM中OC形成的抑制作用强于瘦小鼠。因此,肥胖小鼠BMM中OC形成水平升高可能部分归因于IL-10水平较低,IL-10是破骨细胞生成的负调节因子。我们的研究结果表明,肥胖与骨丢失通过增强破骨细胞生成由于减少IL-10生产的BMM从肥胖小鼠。J.营养139:502-506,2009.
Obesity induces a low-grade systemic chronic inflammatory condition for which macrophages are responsible. We hypothesized that obesity affects osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for 13 wk. We found that the density of the femurs of obese mice was significantly lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by the BMM from obese mice than by those from lean mice upon stimulation of receptor activator of nuclear factor-kappa B ligand. Neutralization of IL-10 in the BMM from obese mice was not as effective in increasing osteoclast (OC) formation as that in those from lean mice. Exogenous IL-10 inhibited OC formation more strongly in the BMM from obese mice than those from lean mice. The elevated level of OC formation in the BMM from obese mice may thus be due to in part to the lower level of IL-10, a negative regulator of osteoclastogenesis. Our results suggest that obesity is associated with bone loss via enhanced osteoclastogenesis due to reduced IL-10 production by the BMM from obese mice. J. Nutr. 139: 502-506, 2009.