Yu Mingzhu, Tian Huan, Lu Ruqing, Quan Ni, Qian Ling
School of Stomatology, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China.
J Periodontal Res. 2024 Dec 1. doi: 10.1111/jre.13368.
Periodontitis is a chronic disease affecting adult oral health. Transient receptor potential vanilloid 1 (TRPV1) expression is shown to upregulate in many inflammatory diseases. Nevertheless, its biological potential along with the molecular mechanism in periodontitis is unclear. Our study aimed to explore the biological role and underlying signaling pathway of TRPV1 in periodontitis.
In the current research, human periodontal ligament stem cells (hPDLSCs) were stimulated by lipopolysaccharide (LPS) to induce inflammatory conditions in vitro. In vivo, the periodontitis mouse model was built by ligating the gingival sulcus of male C57BL/6J mice. Thereafter, the proliferation, apoptosis, inflammation, and oxidative stress-related processes were assessed.
We found that LPS induced apoptosis and inflammation in hPDLCs, along with oxidative stress, while simultaneously inhibiting hPDLC proliferation (p < 0.05). Notably, TRPV1 expression was elevated in LPS-treated hPDLSCs and gingival samples from patients with periodontitis. Interestingly, the increase in TRPV1 expression induced by Capsaicin, a TRPV1 agonist, inhibited cell proliferation while promoting LPS-stimulated apoptosis, inflammation, and oxidative stress in hPDLSCs (p < 0.01). In contrast, inhibition of TRPV1 expression using Capsazepine, a TRPV1 inhibitor, produced opposite effects (p < 0.01). In vivo experiments revealed that inhibition of TRPV1 attenuated ligation-induced periodontitis in mice, as evidenced by enhanced oxidative stress, inflammatory response, and elevated apoptosis (p < 0.01). Additionally, rescue assays indicated that TRPV1 promoted periodontitis-associated tissue inflammation and oxidative damage via activating the STAT3 signaling pathway (p < 0.01).
Our study demonstrates that TRPV1 expression is high in periodontitis and facilitates periodontitis-associated tissue inflammation and oxidative damage by regulating STAT3 signaling pathway, which implies that TRPV1 may represent a new therapeutic target for periodontitis.
牙周炎是一种影响成人口腔健康的慢性疾病。研究表明，瞬时受体电位香草酸受体1（TRPV1）在许多炎症性疾病中表达上调。然而，其在牙周炎中的生物学潜能以及分子机制尚不清楚。我们的研究旨在探讨TRPV1在牙周炎中的生物学作用及潜在信号通路。
在本研究中，使用脂多糖（LPS）刺激人牙周膜干细胞（hPDLSCs）以在体外诱导炎症状态。在体内，通过结扎雄性C57BL/6J小鼠的龈沟建立牙周炎小鼠模型。此后，评估细胞增殖、凋亡、炎症和氧化应激相关过程。
我们发现LPS诱导hPDLCs发生凋亡和炎症，并伴有氧化应激，同时抑制hPDLC增殖（p < 0.05）。值得注意的是，TRPV1在LPS处理的hPDLSCs以及牙周炎患者的牙龈样本中表达升高。有趣的是，TRPV1激动剂辣椒素诱导的TRPV1表达增加抑制了细胞增殖，同时促进了LPS刺激的hPDLSCs凋亡、炎症和氧化应激（p < 0.01）。相反，使用TRPV1抑制剂辣椒平抑制TRPV1表达产生了相反的效果（p < 0.01）。体内实验表明，抑制TRPV1可减轻小鼠结扎诱导的牙周炎，氧化应激增强、炎症反应和凋亡增加证明了这一点（p < 0.01）。此外，挽救实验表明，TRPV1通过激活STAT3信号通路促进牙周炎相关组织炎症和氧化损伤（p < 0.01）。
我们的研究表明，TRPV1在牙周炎中表达升高，并通过调节STAT3信号通路促进牙周炎相关组织炎症和氧化损伤，这意味着TRPV1可能是牙周炎的一个新治疗靶点。
