Huang Jie, Zhang Huang, Fan Xusheng, Wang Yongwu
Department of Stomatology, Hangzhou First People's Hospital Affiliated to West Lake University, No. 261, Huansha Road, Shangcheng District, Hangzhou, Zhejiang, 310006, China.
Clin Oral Investig. 2024 Dec 11;29(1):10. doi: 10.1007/s00784-024-06087-2.
Inflammation and osteoclast activity are important in various diseases, including periodontitis and osteoporosis. Farnesoid X receptor (FXR) has been identified as a promising target for modulating these processes. This study delved into the impact of FXR agonists on inflammation and periodontal regeneration using periodontitis models.
The RAW264.7 and gingival fibroblast cells were divided into five groups: control, lipopolysaccharide (LPS), LPS combined with FXR agonist, LPS with si-FXR, and LPS with si-FXR alongside FXR agonist. FXR expression and pro-inflammatory cytokine levels were quantified. Osteoclast activity was evaluated by observing morphological alterations and tartrate-resistant acid phosphatase staining. The rats were used to establish periodontitis models and received varying doses of FXR agonist. Bone health metrics were assessed, and the expressions of runt-related transcription factor 2 (RUNX2), integrin-binding sialoprotein (IBSP), nuclear factor-kappa B (NF-kB), phosphorylated nuclear factor-kappa B (p-NF-kB), toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) were determined.
FXR suppressed the release of pro-inflammatory cytokines in both LPS-stimulated RAW264.7 and gingival fibroblast cells, while curbing osteoclastogenesis. In periodontitis rat models, FXR agonist administration caused notable enhancement in bone density. Moreover, FXR agonist mitigated periodontal inflammation, decreased periodontal index markers and suppressed the expressions of NF-kB, p-NF-kB, TLR4, and TLR2, but upregulated the expressions of RUNX2 and IBSP.
The data underscores the potential of FXR agonists in attenuating inflammation and periodontal regeneration, both in vitro and in vivo. This suggests the potential therapeutic application of FXR agonists in conditions marked by inflammation and bone degradation.
炎症和破骨细胞活性在包括牙周炎和骨质疏松症在内的多种疾病中都很重要。法尼酯X受体（FXR）已被确定为调节这些过程的一个有前景的靶点。本研究利用牙周炎模型深入探讨了FXR激动剂对炎症和牙周再生的影响。
将RAW264.7细胞和牙龈成纤维细胞分为五组：对照组、脂多糖（LPS）组、LPS联合FXR激动剂组、LPS加si-FXR组以及LPS加si-FXR并联合FXR激动剂组。对FXR表达和促炎细胞因子水平进行定量分析。通过观察形态学改变和抗酒石酸酸性磷酸酶染色来评估破骨细胞活性。使用大鼠建立牙周炎模型，并给予不同剂量的FXR激动剂。评估骨骼健康指标，并测定 runt相关转录因子2（RUNX2）、整合素结合唾液酸蛋白（IBSP）、核因子κB（NF-κB）、磷酸化核因子κB（p-NF-κB）、Toll样受体4（TLR4）和Toll样受体2（TLR2）的表达。
FXR抑制了LPS刺激的RAW264.7细胞和牙龈成纤维细胞中促炎细胞因子的释放，同时抑制了破骨细胞生成。在牙周炎大鼠模型中，给予FXR激动剂可显著提高骨密度。此外，FXR激动剂减轻了牙周炎症，降低了牙周指数标志物，并抑制了NF-κB、p-NF-κB、TLR4和TLR2的表达，但上调了RUNX2和IBSP的表达。
数据强调了FXR激动剂在体外和体内减轻炎症和促进牙周再生的潜力。这表明FXR激动剂在以炎症和骨降解为特征的疾病中具有潜在的治疗应用价值。
