Department of Prosthodontics, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
J Dent Res. 2023 Sep;102(10):1141-1151. doi: 10.1177/00220345231180464. Epub 2023 Jul 18.
Temporomandibular joint osteoarthritis (TMJOA) is a common inflammatory disease that can cause pain, cartilage degradation, and subchondral bone loss. However, the key regulatory factors and new targets for the treatment of TMJOA have yet to be determined. Long noncoding RNAs (lncRNAs) have shown remarkable potential in regulating tissue homeostasis and disease development. The long intergenic RNA-erythroid prosurvival () is reported to be an effective inhibitor of inflammation, but its role in TMJOA is unexplored. Here, we found that is downregulated and negatively correlated with inflammatory factors in the condyles of TMJOA mice. knockout aggravated inflammation and tissue destruction after TMJOA modeling. The in vitro studies confirmed that loss of facilitated inflammatory factor expression in condylar chondrocytes, while recovered expression of showed anti-inflammatory effects. Mechanistically, RNA sequencing revealed that the inflammatory response pathway nuclear factor-kappa B (NF-κB) was mostly affected by deficiency. Moreover, was proved to effectively bind to serine/arginine-rich splicing factor 3 (SRSF3) and inhibit its function in pyruvate kinase isoform M2 (PKM2) formation, thus restraining the PKM2/NF-κB pathway and the expression of inflammatory factors. In addition, local injection of the overexpression lentivirus significantly alleviated inflammation, cartilage degradation, and subchondral bone loss in TMJOA mice. Overall, regulated the inflammatory process of condylar chondrocytes by binding to SRSF3 and showed translational application potential in the treatment of TMJOA.
颞下颌关节骨关节炎（TMJOA）是一种常见的炎症性疾病，可引起疼痛、软骨降解和软骨下骨丢失。然而，TMJOA 治疗的关键调节因子和新靶点尚未确定。长链非编码 RNA（lncRNA）在调节组织稳态和疾病发展方面表现出显著的潜力。长间隔 RNA-红细胞生存（）被报道为一种有效的炎症抑制剂，但它在 TMJOA 中的作用尚未被探索。在这里，我们发现 在 TMJOA 小鼠髁突中下调，并与炎症因子呈负相关。 基因敲除加剧了 TMJOA 模型建立后的炎症和组织破坏。体外研究证实，丧失 促进了髁状突软骨细胞中炎症因子的表达，而恢复 的表达则表现出抗炎作用。机制上，RNA 测序显示炎症反应途径核因子-κB（NF-κB）受 缺失的影响最大。此外，证明 可有效结合丝氨酸/精氨酸丰富剪接因子 3（SRSF3）并抑制其在丙酮酸激酶同工酶 M2（PKM2）形成中的功能，从而抑制 PKM2/NF-κB 途径和炎症因子的表达。此外，局部注射 过表达慢病毒显著缓解了 TMJOA 小鼠的炎症、软骨降解和软骨下骨丢失。总之， 通过与 SRSF3 结合调节髁状突软骨细胞的炎症过程，在 TMJOA 的治疗中显示出转化应用的潜力。
