Li Yanyan, Sun Huifang, Liu Xin, Hu Zhihui, Jiang Henghua, Guo Huilin, Long Xing
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Int Immunopharmacol. 2023 Jan;114:109486. doi: 10.1016/j.intimp.2022.109486. Epub 2022 Dec 9.
The temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive cartilage degradation, subchondral bone erosion, and chronic pain, leading to articular damage and chewing dysfunction. Studies have shown that interleukin-1β (IL-1β) plays a critical role in the development of TMJ-OA. Transglutaminase 2 (TG2) has been identified as a marker of chondrocyte hypertrophy and IL-1β was able to increase TG2 expression in chondrocytes. Therefore, the aim of this study was to explore the ability of TG2 inhibitors to suppress TMJ-OA progression.
Firstly, toluidine blue staining, cell counting kit-8 assay, immunocytofluorescent staining and western blot were used to investigate the anti-inflammatory effects of TG2 inhibitors in IL-1β-stimulated murine chondrocytes and the underlying mechanisms. Afterwards, micro-CT analysis, histological staining, immunohistochemical and immunohistofluorescent staining were used to evaluate the therapeutic efficacy of TG2 inhibitors in monosodium iodoacetate (MIA)-induced TMJ-OA in rats.
TG2 inhibitors suppressed the IL-1β-induced upregulation of COX-2, iNOS, MMP-13, and MMP-3 and reversed the IL-1β-induced proteoglycan loss in chondrocytes through inhibiting NF-κB activation. Consistently, the MIA-induced upregulation of MMP-13 and MMP-3, and loss of structural integrity of the articular cartilage and subchondral bone were markedly reversed by TG2 inhibitors via inhibiting NF-κB activation.
TG2 inhibitors demonstrated a potent therapeutic efficacy on cartilage and subchondral bone structures of TMJ-OA by reducing inflammation and cartilage degradation through suppressing NF-κB activation.
颞下颌关节骨关节炎（TMJ - OA）的特征是软骨进行性退化、软骨下骨侵蚀和慢性疼痛，导致关节损伤和咀嚼功能障碍。研究表明，白细胞介素 - 1β（IL - 1β）在TMJ - OA的发展中起关键作用。转谷氨酰胺酶2（TG2）已被确定为软骨细胞肥大的标志物，并且IL - 1β能够增加软骨细胞中TG2的表达。因此，本研究的目的是探讨TG2抑制剂抑制TMJ - OA进展的能力。
首先，使用甲苯胺蓝染色、细胞计数试剂盒 - 8检测、免疫细胞荧光染色和蛋白质印迹法研究TG2抑制剂在IL - 1β刺激的小鼠软骨细胞中的抗炎作用及其潜在机制。之后，使用显微CT分析、组织学染色、免疫组织化学和免疫荧光染色评估TG2抑制剂在碘乙酸钠（MIA）诱导的大鼠TMJ - OA中的治疗效果。
TG2抑制剂通过抑制NF - κB活化，抑制了IL - 1β诱导的COX - 2、iNOS、MMP - 13和MMP - 3的上调，并逆转了IL - 1β诱导的软骨细胞中蛋白聚糖的损失。同样，TG2抑制剂通过抑制NF - κB活化，显著逆转了MIA诱导的MMP - 13和MMP - 3的上调以及关节软骨和软骨下骨结构完整性的丧失。
TG2抑制剂通过抑制NF - κB活化来减轻炎症和软骨降解，从而对TMJ - OA的软骨和软骨下骨结构显示出有效的治疗效果。
