Wu Huan-Huan, Guo Yuan, Pu Yin-Fei, Tang Zhi-Hui
Second Dental Center, School and Hospital of Stomatology, Peking University, Beijing 100081, People's Republic of China.
National Engineering Laboratory for Digital and Material Technology of Stomatology, School and Hospital of Stomatology, Peking University, Beijing 100081, People's Republic of China.
Biosci Rep. 2021 Mar 26;41(3). doi: 10.1042/BSR20192668.
Periodontal diseases are infections of the structures that surround and support the teeth; they are characterized by local inflammation and alveolar bone loss. Most treatments focus on only one aspect, inhibiting inflammation, or promoting osteoblasts. We set out to develop a new method that would intervene in the two aspects simultaneously. Adiponectin (APN), secreted by adipocytes, inhibits the inflammatory response and promotes osteogenesis. However, its role in human periodontal ligament cells (hPDLCs) is unclear. Therefore, we aim to investigate whether APN could suppress lipopolysaccharide (LPS)-induced inflammation and promote osteogenesis in hPDLCs. In the present study, we stimulated hPDLCs with LPS in the presence or absence of APN. Real-time PCR and Western blotting results demonstrated that APN partially inhibited the activation of the classical nuclear factor κ-B (NF-κB) pathway. These results were confirmed by a change of expressions of NF-κB downstream inflammatory genes, such as decreased cyclooxygenase (COX)-2 and tumor necrosis factor α (TNF-α), along with increased interleukin (IL)-10. As for the role of APN in osteogenesis, Alizarin Red S staining showed that APN treatment induced more calcium deposition nodules than controls. We also found that APN enhanced the expression of osteoblast-related genes (osteopontin (OPN), collagen 1, osteocalcin, alkaline phosphatase, runt-related transcription factor 2 (RUNX2), and bone morphogenetic protein 2) in hPDLCs via the APPL1 (the adaptor protein containing PH domain, PTB domain, and leucine zipper motif 1)/p38 signal transduction pathway. Therefore, APN inhibits LPS-induced inflammation and promotes osteogenesis in hPDLCs and may have potential therapeutic value in treating periodontitis by inhibiting the inflammatory lesions and contributing to bone tissue regeneration.
牙周疾病是牙齿周围和支持结构的感染性疾病；其特征是局部炎症和牙槽骨丧失。大多数治疗仅关注一个方面，即抑制炎症或促进成骨细胞生成。我们着手开发一种能同时干预这两个方面的新方法。脂联素（APN）由脂肪细胞分泌，可抑制炎症反应并促进骨生成。然而，其在人牙周膜细胞（hPDLCs）中的作用尚不清楚。因此，我们旨在研究APN是否能抑制脂多糖（LPS）诱导的hPDLCs炎症并促进其成骨。在本研究中，我们在有或无APN的情况下用LPS刺激hPDLCs。实时PCR和蛋白质印迹结果表明，APN部分抑制了经典核因子κB（NF-κB）途径的激活。NF-κB下游炎症基因表达的变化证实了这些结果，如环氧合酶（COX）-2和肿瘤坏死因子α（TNF-α）减少，同时白细胞介素（IL）-10增加。至于APN在成骨中的作用，茜素红S染色显示，与对照组相比，APN处理诱导产生了更多的钙沉积结节。我们还发现，APN通过APPL1（含PH结构域、PTB结构域和亮氨酸拉链基序1的衔接蛋白）/p38信号转导途径增强了hPDLCs中成骨细胞相关基因（骨桥蛋白（OPN）、胶原蛋白1、骨钙素、碱性磷酸酶、 runt相关转录因子2（RUNX2）和骨形态发生蛋白2）的表达。因此，APN抑制LPS诱导的hPDLCs炎症并促进其成骨，可能在通过抑制炎症病变和促进骨组织再生来治疗牙周炎方面具有潜在的治疗价值。
