Department of Physiology, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
Department of Developmental and Regenerative Dentistry, School of Life Dentistry at Tokyo, The Nippon Dental University, Japan; Department of Life Science Dentistry, The Nippon Dental University, Japan.
Life Sci. 2024 Oct 15;355:123009. doi: 10.1016/j.lfs.2024.123009. Epub 2024 Aug 26.
Adipose tissue dysfunction is a key feature of metabolic syndrome, which increases the risk of periodontitis, an inflammatory disease induced by bacteria that affects the gingiva and other components of periodontal tissue. Recent studies indicate that molecules from inflamed periodontal tissue contribute to adipose tissue dysfunction. However, the cellular mechanisms and interactions between adipose tissue and gingiva driving the progression of metabolic and periodontal conditions remain unclear. To address this, we developed a chimeric (mouse/human) co-culture tissue model (which identifies the origins of species-specific cytokines) to investigate these interactions. Using tissue-specific functional cells and immunocytes, we constructed equivalents of adipose tissue (ATE) and gingiva (GTE), co-cultivating them under inflammatory conditions induced by bacterial endotoxin, lipopolysaccharide (LPS). Our findings showed that exposure to LPS resulted in a notable reduction in lipid accumulation, GLUT4 expression, and adiponectin secretion in ATE, along with increased macrophage colonies forming around lipid droplets, as well as elevated levels of triglyceride, leptin, and IL-6. In GTE, LPS triggered significant inflammatory responses, characterized by increased macrophage accumulation, elevated COX-2 expression, and heightened secretion of inflammatory cytokines. LPS also reduced epithelial thickness and the expression of keratin 19 and collagen IV, indicating impaired barrier function and gingival integrity. Co-culturing ATE with GTE exacerbated these LPS-induced harmful effects in both tissues. In conclusion, our findings suggest that interplay between gingiva and adipose tissue can intensify the inflammatory and dysfunctional changes caused by LPS. This co-culture tissue model offers a valuable tool for future studies on periodontitis and metabolic syndrome.
脂肪组织功能障碍是代谢综合征的一个关键特征，它会增加牙周炎的风险，牙周炎是一种由细菌引起的炎症性疾病，影响牙龈和牙周组织的其他成分。最近的研究表明，来自发炎的牙周组织的分子有助于脂肪组织功能障碍。然而，脂肪组织和牙龈之间导致代谢和牙周状况进展的细胞机制和相互作用仍不清楚。为了解决这个问题，我们开发了一种嵌合（小鼠/人）共培养组织模型（可识别种特异性细胞因子的来源）来研究这些相互作用。使用组织特异性功能细胞和免疫细胞，我们构建了脂肪组织（ATE）和牙龈（GTE）的等效物，在细菌内毒素脂多糖（LPS）诱导的炎症条件下对它们进行共培养。我们的研究结果表明，暴露于 LPS 导致 ATE 中的脂质积累、GLUT4 表达和脂联素分泌明显减少，同时在脂滴周围形成的巨噬细胞菌落增加，以及甘油三酯、瘦素和 IL-6 水平升高。在 GTE 中，LPS 引发了明显的炎症反应，表现为巨噬细胞积累增加、COX-2 表达上调和炎症细胞因子分泌增加。LPS 还降低了上皮厚度和角蛋白 19 和胶原 IV 的表达，表明屏障功能和牙龈完整性受损。ATE 与 GTE 共培养加剧了这两种组织中 LPS 诱导的有害影响。总之，我们的研究结果表明，牙龈和脂肪组织之间的相互作用可以加剧 LPS 引起的炎症和功能障碍变化。这种共培养组织模型为牙周炎和代谢综合征的未来研究提供了有价值的工具。
