Although there is a clear relationship between the degree of obesity and periodontal disease incidence, the mechanisms that underpin the links between these conditions are not completely understood. Understanding that myeloid-derived suppressor cells (MDSCs) are expanded during obesity and operate in a context-defined manner, we addressed the potential role of MDSCs to contribute toward obesity-associated periodontal disease. Flow cytometry revealed that in the spleen of mice fed a high-fat diet (HFD), expansion in monocytic MDSCs (M-MDSCs) significantly increased when compared with mice fed a low-fat diet (LFD). In the osteoclast differentiation assay, M-MDSCs isolated from the bone marrow of HFD-fed mice showed a larger number and area of osteoclasts with a greater number of nuclei. In the M-MDSCs of HFD-fed mice, several osteoclast-related genes were significantly elevated when compared with LFD-fed mice according to a focused transcriptomic platform. In experimental periodontitis, the number and percentage of M-MDSCs were greater, with a significantly larger increase in HFD-fed mice versus LFD-fed mice. In the spleen, the percentage of M-MDSCs was significantly higher in HFD-fed periodontitis-induced (PI) mice than in LFD-PI mice. Alveolar bone volume fraction was significantly reduced in experimental periodontitis and was further decreased in HFD-PI mice as compared with LFD-PI mice. The inflammation score was significantly higher in HFD-PI mice versus LFD-PI mice, with a concomitant increase in TRAP staining for osteoclast number and area in HFD-PI mice over LFD-PI mice. These data support the concept that M-MDSC expansion during obesity to become osteoclasts during periodontitis is related to increased alveolar bone destruction, providing a more detailed mechanistic appreciation of the interconnection between obesity and periodontitis.

尽管肥胖程度与牙周病发病率之间存在明确的关系，但支持这些疾病之间联系的机制尚不完全清楚。了解骨髓来源的抑制细胞 (MDSCs) 在肥胖过程中会扩张并以特定的方式运作，我们探讨了 MDSCs 在导致肥胖相关牙周病方面的潜在作用。流式细胞术显示，与喂食低脂饮食 (LFD) 的小鼠相比，在喂食高脂肪饮食 (HFD) 的小鼠脾脏中，单核细胞 MDSCs (M-MDSCs) 的扩增显着增加。在破骨细胞分化试验中，从 HFD 喂养小鼠的骨髓中分离出的 M-MDSCs 显示出更大数量和面积的破骨细胞以及更多的细胞核。在 HFD 喂养小鼠的 M-MDSC 中，根据聚焦的转录组学平台，与 LFD 喂养的小鼠相比，几个破骨细胞相关基因显着升高。在实验性牙周炎中，M-MDSCs 的数量和百分比更大，HFD 喂养的小鼠与 LFD 喂养的小鼠相比显着增加。在脾脏中，M-MDSCs 的百分比在 HFD 喂养的牙周炎诱导 (PI) 小鼠中明显高于 LFD-PI 小鼠。与 LFD-PI 小鼠相比，实验性牙周炎的牙槽骨体积分数显着降低，并且在 HFD-PI 小鼠中进一步降低。HFD-PI 小鼠的炎症评分显着高于 LFD-PI 小鼠，同时 HFD-PI 小鼠破骨细胞数量和面积的 TRAP 染色比 LFD-PI 小鼠增加。