Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice.
Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice.
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DOI：
10.1016/j.exger.2010.09.014
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发表时间：
2011-01
影响因子：
3.9
通讯作者：
Fernandes, Gabriel
中科院分区：
文献类型：
--
作者：
Halade, Ganesh V.;El Jamali, Amina;Williams, Paul J.;Fajardo, Roberto J.;Fernandes, Gabriel
临床证据表明，在老年肥胖妇女中，脂肪与骨量成反比。然而，目前尚不清楚肥胖是否会加速骨质流失。在这份报告中，我们提出的证据表明，增加内脏脂肪导致炎症和随后的骨丢失在12个月大的C57 BL/6 J小鼠，喂食10%玉米油（CO）为基础的饮食和对照实验室食物（LC）6个月。正如我们以前的工作所预期的那样，与LC相比，CO喂养的小鼠表现出内脏脂肪增加和全身脂肪量增加。在CO喂养的小鼠中，脂肪细胞特异性PPARγ和骨髓（BM）肥胖增加。与这些变化相关，与LC喂养的小鼠相比，CO喂养的小鼠中的炎性细胞因子（IL-1β、IL-6、TNF-α）显著升高。这种炎症性BM微环境导致破骨细胞和未分化BM细胞中超氧化物产生增加。在CO喂养的小鼠中，每骨小梁长度的破骨细胞数量增加和体外评估的破骨细胞生成增加表明CO饮食诱导骨吸收。此外，破骨细胞特异性组织蛋白酶k和RANKL表达的上调和成骨细胞特异性RUNX 2/Cbfa 1的下调支持CO喂养小鼠的这种骨吸收。此外，COfed小鼠股骨远端干骺端的骨小梁体积较低，OPG表达减少。总的来说，我们的研究结果表明，增加骨吸收的小鼠喂养一氧化碳丰富的饮食可能是由于增加炎症介导的脂肪细胞在BM微环境中的积累。因此，这种炎症可能会增加破骨细胞的生成，同时减少成骨细胞的发展，在CO喂养的小鼠。
Clinical evidence indicates that fat is inversely proportional to bone mass in elderly obese women. However, it remains unclear whether obesity accelerates bone loss. In this report we present evidence that increased visceral fat leads to inflammation and subsequent bone loss in 12-month-old C57BL/6J mice that were fed 10% corn oil (CO)-based diet and a control lab chow (LC) for 6 months. As expected from our previous work, CO-fed mice demonstrated increased visceral fat and enhanced total body fat mass compared to LC. The adipocyte-specific PPARγ and bone marrow (BM) adiposity were increased in CO-fed mice. In correlation with those modifications, inflammatory cytokines (IL-1β, IL-6, TNF-α) were significantly elevated in COfed mice compared to LC-fed mice. This inflammatory BM microenvironment resulted in increased superoxide production in osteoclasts and undifferentiated BM cells. In CO-fed mice, the increased number of osteoclasts per trabecular bone length and the increased osteoclastogenesis assessed ex-vivo suggest that CO diet induces bone resorption. Additionally, the up-regulation of osteoclast-specific cathepsin k and RANKL expression and down-regulation of osteoblast-specific RUNX2/Cbfa1 supports this bone resorption in CO-fed mice. Also, COfed mice exhibited lower trabecular bone volume in the distal femoral metaphysis and had reduced OPG expression. Collectively, our results suggest that increased bone resorption in mice fed a CO-enriched diet is possibly due to increased inflammation mediated by the accumulation of adipocytes in the BM microenvironment. This inflammation may consequently increase osteoclastogenesis, while reducing osteoblast development in CO-fed mice.
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