Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.
Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University-UNESP, Araraquara 14801-385, SP, Brazil.
Int J Mol Sci. 2023 Mar 1;24(5):4733. doi: 10.3390/ijms24054733.
This study aimed to explore effects of with or without apelin on periodontal ligament (PDL) cells to better understand pathomechanistic links between periodontitis and obesity. First, the actions of on COX2, CCL2, and MMP1 expressions were assessed. Subsequently, PDL cells were incubated with in the presence and absence of apelin to study the modulatory effects of this adipokine on molecules related to inflammation and hard and soft tissue turnover. Regulation of apelin and its receptor (APJ) by was also studied. resulted in elevated COX2, CCL2, and MMP1 expressions in a dose- and time-dependent manner. Combination of and apelin led to the highest ( < 0.05) expression levels of COX2, CCL2, CXCL8, TNF-α, and MMP1 at 48 h. The effects of and/or apelin on CCL2 and MMP1 were MEK1/2- and partially NF-κB-dependent. The combined effects of and apelin on CCL2 and MMP1 were also observed at protein level. Moreover, downregulated ( < 0.05) the apelin and APJ expressions. In conclusion, obesity could contribute to periodontitis through apelin. The local production of apelin/APJ in PDL cells also suggests a role of these molecules in the pathogenesis of periodontitis.
本研究旨在探讨脂联素（apelin）及其配体（APJ）在肥胖与牙周炎之间的病理机制联系。首先，研究了脂联素对牙周膜（PDL）细胞中环氧化酶 2（COX2）、趋化因子配体 2（CCL2）和基质金属蛋白酶 1（MMP1）表达的作用。随后，在有无脂联素存在的情况下，将 PDL 细胞与脂联素孵育，以研究这种脂肪因子对与炎症和软硬组织转化相关的分子的调节作用。同时也研究了脂联素及其受体（APJ）对 的调节作用。结果表明，脂联素呈剂量和时间依赖性地增加 COX2、CCL2 和 MMP1 的表达。脂联素和脂联素联合使用 48 小时后，COX2、CCL2、CXCL8、TNF-α 和 MMP1 的表达水平达到最高（<0.05）。脂联素和/或脂联素对 CCL2 和 MMP1 的作用部分依赖于丝裂原活化蛋白激酶 1/2（MEK1/2）和核因子-κB（NF-κB）。在蛋白水平上也观察到了脂联素和脂联素对 CCL2 和 MMP1 的联合作用。此外，脂联素还下调了 apelin 和 APJ 的表达。综上所述，肥胖可能通过脂联素促进牙周炎的发生。PDL 细胞中脂联素/APJ 的局部产生也表明这些分子在牙周炎发病机制中的作用。
