Guangdong Provincial Key Laboratory of Stomatology, Stomatology Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China.
Mol Med Rep. 2020 Aug;22(2):1195-1204. doi: 10.3892/mmr.2020.11193. Epub 2020 May 28.
Interleukin (IL)‑1β is a key promotor in the pathogenesis of temporomandibular joint osteoarthritis. Differentiation of stem cells to cartilage is a crucial repair mechanism of articular cartilage damage, and IL‑1β has been reported to impede the differentiation by upregulating the secretion of IL‑6, an important inflammatory factor. Long non‑coding RNAs (lncRNAs) regulate a number of physiological and pathological processes, but whether lncRNA AK094629 contributes to the IL‑1β mediated induction of inflammation remains unclear. Therefore, the aim of the present study was to investigate the effect of AK094629 on IL‑1β‑induced IL‑6 expression in synovial‑derived mesenchymal stem cells (SMSCs) of the temporomandibular joints. The results of the present study demonstrated that the expression of AK094629 in the synovial tissue of patients with osteoarthritis was positively correlated with IL‑1β. In addition, IL‑1β upregulated the expression of AK094629 in the SMSCs in vitro, and AK094629 knockdown inhibited the IL‑1β mediated upregulation of IL‑6. The present study also demonstrated that AK094629 knockdown downregulated the expression of the mitogen‑activated protein kinase kinase kinase 4 (MAP3K4), which is upregulated by IL‑1β, whereas knockdown of MAP3K4 did not affect the expression of AK094629, but reversed the upregulation of IL‑6 in SMSCs. In conclusion, AK094629 knockdown attenuated the expression of IL‑1β‑regulated IL‑6 in the SMSCs of the temporomandibular joint by inhibiting MAP3K4. Therefore, AK094629 may be a potential novel therapeutic target for the treatment of temporomandibular joint osteoarthritis.
白细胞介素 (IL)‑1β 是颞下颌关节骨关节炎发病机制中的关键促进因子。干细胞向软骨的分化是关节软骨损伤的重要修复机制,据报道,IL‑1β 通过上调重要炎症因子 IL‑6 的分泌来阻碍分化。长链非编码 RNA(lncRNA)调节许多生理和病理过程,但 lncRNA AK094629 是否有助于 IL‑1β 介导的炎症诱导尚不清楚。因此,本研究旨在探讨 AK094629 对 IL‑1β 诱导的颞下颌关节滑膜间充质干细胞(SMSCs)中 IL‑6 表达的影响。本研究结果表明,骨关节炎患者滑膜组织中 AK094629 的表达与 IL‑1β 呈正相关。此外,IL‑1β 在体外上调 SMSCs 中 AK094629 的表达,AK094629 敲低抑制了 IL‑1β 介导的 IL‑6 上调。本研究还表明,AK094629 敲低下调了 MAP3K4 的表达,MAP3K4 是由 IL‑1β 上调的,而 MAP3K4 的敲低不影响 AK094629 的表达,但逆转了 SMSCs 中 IL‑6 的上调。综上所述,AK094629 敲低通过抑制 MAP3K4 减弱了 IL‑1β 调节的 SMSCs 中 IL‑6 的表达,因此,AK094629 可能是治疗颞下颌关节骨关节炎的潜在新治疗靶点。