Leypold Tim, Herbsthofer Alix, Craveiro Rogerio B, Wolf Michael, Beier Justus P, Ruhl Tim
Department of Plastic Surgery, Hand Surgery-Burn Center, University Hospital RWTH Aachen, Aachen, Germany.
Department of Orthodontics, University Hospital RWTH Aachen, Aachen, Germany.
J Periodontal Implant Sci. 2025 Feb;55(1):18-34. doi: 10.5051/jpis.2303680184. Epub 2024 Jul 15.
Periodontitis is an inflammatory disease that results in the loss of periodontal tissue. The endocannabinoid system has anti-inflammatory properties and displays considerable potential for tissue regeneration. In this study, we aimed to explore whether the activation of this system can alleviate or reverse the inflammatory phenotype of human periodontal ligament stem cells (hPDLSCs) induced by exposure to the inflammagen lipopolysaccharide (LPS).
We investigated the effects of activating specific cannabinoid receptors (CB1 and CB2) on the inflammatory phenotype of LPS-stimulated hPDLSCs. The exogenous ligands WIN55,212-2 and JWH-133 were employed to target the cannabinoid receptors. We conducted a thorough assessment of cell proliferation, metabolic activity, and adipogenic, osteogenic, and chondrogenic differentiation potential. Additionally, we measured cytokine release using enzyme-linked immunosorbent assays.
Exposure to lipopolysaccharide (Pg-LPS) caused an increase in cell proliferation while decreasing metabolic activity. While this exposure did not influence adipogenic or chondrogenic differentiation, it did result in reduced osteogenesis. Additionally, LPS induced the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein 1. Immunolabeling revealed the presence of CB1 and CB2 on the cellular membrane, with these receptors playing distinct roles in hPDLSCs. The CB1 agonist WIN55,212-2 was found to increase metabolic activity and promote adipogenic differentiation, whereas the CB2 agonist JWH-133 promoted cell proliferation and osteogenic differentiation. When hPDLSCs were co-exposed to Pg-LPS and CB ligands, JWH-133 slightly ameliorated the inhibition of osteogenic differentiation and suppressed the release of inflammatory cytokines.
This study clarifies the effects of specific CB receptor activation on hPDLCs and the inflammatory phenotype. Stimulation of the endocannabinoid system through the manipulation of endogenous or the application of exogenous cannabinoids may represent a potent therapeutic option for combating periodontal inflammatory disorders.
牙周炎是一种导致牙周组织丧失的炎症性疾病。内源性大麻素系统具有抗炎特性，并显示出相当大的组织再生潜力。在本研究中，我们旨在探讨该系统的激活是否能减轻或逆转暴露于炎症原脂多糖（LPS）诱导的人牙周膜干细胞（hPDLSCs）的炎症表型。
我们研究了激活特定大麻素受体（CB1和CB2）对LPS刺激的hPDLSCs炎症表型的影响。使用外源性配体WIN55,212-2和JWH-133作用于大麻素受体。我们对细胞增殖、代谢活性以及成脂、成骨和软骨分化潜能进行了全面评估。此外，我们使用酶联免疫吸附测定法测量细胞因子释放。
暴露于牙龈卟啉单胞菌脂多糖（Pg-LPS）会导致细胞增殖增加，同时代谢活性降低。虽然这种暴露不影响成脂或软骨分化，但确实导致成骨减少。此外，LPS诱导白细胞介素（IL）-6、IL-8和单核细胞趋化蛋白1的释放。免疫标记显示细胞膜上存在CB1和CB2，这些受体在hPDLSCs中发挥不同作用。发现CB1激动剂WIN55,212-2可增加代谢活性并促进成脂分化，而CB2激动剂JWH-133促进细胞增殖和成骨分化。当hPDLSCs同时暴露于Pg-LPS和CB配体时，JWH-133略微改善了对成骨分化的抑制并抑制了炎症细胞因子的释放。
本研究阐明了特定CB受体激活对hPDLCs及其炎症表型的影响。通过操纵内源性或应用外源性大麻素来刺激内源性大麻素系统可能是对抗牙周炎症性疾病的一种有效治疗选择。
