The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Affiliated Stomatological Hospital of Nanchang University, Nanchang, China.
J Cell Mol Med. 2022 Feb;26(3):925-936. doi: 10.1111/jcmm.17149. Epub 2021 Dec 24.
To investigate the role of glycyrrhizin on the progression of temporomandibular joint osteoarthritis (TMJOA) and the underlying mechanism by regulation of the high-mobility group box 1 (HMGB1) receptor for advanced glycation end products (RAGE)/toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB)/protein kinase B (AKT) pathway. After a rat model of TMJOA was built by intra-articular injection of monosodium iodoacetate, glycyrrhizin was intragastrically administered at low concentration (20 mg/kg) or high concentration (50 mg/kg). Micro-computed tomography, histological and immunohistochemical analysis were used to reveal the progression of TMJOA. Rat TMJ chondrocytes and disc cells were cultured in inflammatory condition with different doses of glycyrrhizin. Western blot was used to evaluate the effect of glycyrrhizin on the HMGB1-RAGE/TLR4-NF-κB/AKT pathway. Administration of glycyrrhizin alleviated cartilage degeneration, lowered the levels of inflammatory and catabolic mediators and reduced the production of HMGB1, RAGE and TLR4 in TMJOA animal model. Increased production of RAGE and TLR4, and activated intracellular NF-κB and/or AKT signalling pathways in chondrocytes and disc cells were found in inflammatory condition. Upon activation, matrix metalloprotease-3 and interleukin-6 were upregulated. Glycyrrhizin inhibited not only HMGB1 release but also RAGE and TLR4 in inflammatory condition. Glycyrrhizin alleviated the pathological changes of TMJOA by regulating the HMGB1-RAGE/TLR4-NF-kB/AKT signalling pathway. This study revealed the potential of glycyrrhizin as a novel therapeutic drug to suppress TMJ cartilage degradation.
探讨甘草酸通过调控高迁移率族蛋白 1（HMGB1）受体-晚期糖基化终产物（RAGE）/Toll 样受体 4（TLR4）-核因子 κB（NF-κB）/蛋白激酶 B（AKT）通路对颞下颌关节骨关节炎（TMJOA）进展的作用及其机制。
通过关节腔内注射单碘乙酸钠构建大鼠 TMJOA 模型，分别给予低浓度（20mg/kg）和高浓度（50mg/kg）甘草酸灌胃。采用 micro-CT、组织学和免疫组织化学分析揭示 TMJOA 的进展。将大鼠 TMJ 软骨细胞和盘细胞在不同剂量甘草酸的炎症条件下培养，采用 Western blot 评估甘草酸对 HMGB1-RAGE/TLR4-NF-κB/AKT 通路的影响。
甘草酸减轻了软骨退变，降低了炎症和分解代谢介质的水平，并减少了 TMJOA 动物模型中 HMGB1、RAGE 和 TLR4 的产生。在炎症条件下，软骨细胞和盘细胞中 RAGE 和 TLR4 的产生增加，细胞内 NF-κB 和/或 AKT 信号通路被激活，基质金属蛋白酶-3 和白细胞介素-6 上调。甘草酸不仅抑制 HMGB1 的释放，而且在炎症条件下还抑制 RAGE 和 TLR4。甘草酸通过调节 HMGB1-RAGE/TLR4-NF-κB/AKT 信号通路缓解 TMJOA 的病理变化。
本研究揭示了甘草酸作为一种抑制 TMJ 软骨降解的新型治疗药物的潜力。
