Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, Korea.
Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, Korea.
J Periodontal Res. 2019 Dec;54(6):690-701. doi: 10.1111/jre.12678. Epub 2019 Jul 21.
Dietary bioactive materials having anti-inflammatory and antioxidant potentials are able to inhibit diabetes-associated periodontal complications. Although numerous studies indicate that administration of p-coumaric acid (p-CA) ameliorates diabetes and diabetes-related complications, the roles of p-CA on periodontal tissue destruction in diabetic mice and the possible mechanisms therein are not completely understood. In this study, we evaluated whether supplementation with p-CA protects mice against diabetes-associated spontaneous periodontal destruction and also explored the associated mechanism therein using in vivo and in vitro experimental systems.
C57BL/6 male mice were divided into sham, streptozotocin (STZ), and STZ+CA groups (n = 5/group). Sham group was intraperitoneally injected with sodium buffer, whereas other two groups were injected with the buffer containing 160 mg/kg of STZ. STZ-induced diabetic mice received oral gavage with p-CA (50 mg/kg) (STZ+CA group) or with buffer only (STZ group) daily for 6 weeks. The effect of p-CA on diabetes-associated spontaneous periodontal destruction was evaluated using μCT analysis, hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, and immunohistochemical staining methods. The efficacies of p-CA on cell proliferation, osteoblast differentiation, reactive oxygen species (ROS) accumulation, and antioxidant-related marker expression were examined using human periodontal ligament fibroblasts (hPLFs) cultured under high glucose condition.
Streptozotocin group exhibited periodontal tissue destruction along with increased inflammation, oxidative stress, and osteoclast formation, as well as with decreased osteogenesis. However, oral administration with p-CA protected mice against STZ-induced periodontal destruction by inhibiting inflammation and osteoclastic activation. STZ+CA group also showed higher expression of antioxidant and osteogenic markers in periodontal tissue than did STZ group. Treatment with high glucose concentration (30 mmol/L) impaired proliferation and osteoblast differentiation of hPLFs along with cellular ROS accumulation, whereas these impairments were almost completely disappeared by supplementation with p-CA.
These findings demonstrate that supplementation with p-CA inhibits diabetes-associated spontaneous destruction of periodontal tissue by enhancing anti-inflammatory, anti-osteoclastogenic, and antioxidant defense systems in STZ-treated mice.
具有抗炎和抗氧化潜力的膳食生物活性物质能够抑制与糖尿病相关的牙周并发症。虽然许多研究表明对 p-香豆酸（p-CA）的给药可以改善糖尿病和与糖尿病相关的并发症，但 p-CA 对糖尿病小鼠牙周组织破坏的作用及其可能的机制尚不完全清楚。在这项研究中，我们评估了 p-CA 的补充是否可以保护小鼠免受与糖尿病相关的自发性牙周破坏，并使用体内和体外实验系统探讨了其中的相关机制。
将 C57BL/6 雄性小鼠分为假手术组、链脲佐菌素（STZ）组和 STZ+CA 组（每组 n=5）。假手术组经腹腔注射生理盐水，而其他两组则注射含 160mg/kg STZ 的缓冲液。STZ 诱导的糖尿病小鼠每日口服灌胃 p-CA（50mg/kg）（STZ+CA 组）或仅用缓冲液灌胃（STZ 组），共 6 周。使用μCT 分析、苏木精和伊红染色、抗酒石酸酸性磷酸酶染色和免疫组织化学染色方法评估 p-CA 对与糖尿病相关的自发性牙周破坏的影响。使用高糖条件下培养的人牙周韧带成纤维细胞（hPLFs）检查 p-CA 对细胞增殖、成骨分化、活性氧（ROS）积累和抗氧化相关标志物表达的功效。
STZ 组表现出牙周组织破坏，伴有炎症、氧化应激和破骨细胞形成增加，以及成骨减少。然而，口服 p-CA 可通过抑制炎症和破骨细胞激活来保护小鼠免受 STZ 诱导的牙周破坏。STZ+CA 组牙周组织中的抗氧化和成骨标志物表达也高于 STZ 组。高浓度葡萄糖（30mmol/L）处理会损害 hPLFs 的增殖和成骨分化，同时导致细胞内 ROS 积累，而补充 p-CA 几乎完全消除了这些损伤。
这些发现表明，p-CA 的补充通过增强 STZ 处理小鼠的抗炎、抗破骨细胞生成和抗氧化防御系统来抑制与糖尿病相关的自发性牙周组织破坏。
