Synovium-derived mesenchymal stem cells (SMSCs) can migrate to the site of destroyed condylar cartilage and differentiate into chondrocytes to repair temporomandibular joint (TMJ) damage. Interleukin (IL)-1β-induced IL-6 secretion has been shown to inhibit the chondrogenic potential of SMSCs. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) has recently been shown to be closely related to the inflammation induced by IL-1β. However, the relationship between SAHA and IL-6 secretion induced by IL-1β in SMSCs remains unclear. In this study, we evaluated the relationships between IL-1β and IL-6 in synovial specimens from patients with TMD and in model rats with osteoarthritis (OA). We found that IL-1β and IL-6 were positively correlated and that IL-6 expression in SMSCs increased with IL-1β stimulation in vitro. Moreover, microtubule affinity-regulating kinase 4 (MARK4) was significantly upregulated in IL-1β-stimulated SMSCs and in the synovium of rats with OA. MARK4 knockdown inhibited IL-6 secretion and nuclear factor (NF)-κB pathway activation in IL-1β-stimulated SMSCs. SAHA attenuated IL-6 secretion in IL-1β-induced SMSCs through NF-κB pathway inhibition, and MARK4 was also downregulated in SAHA-treated SMSCs. However, inhibition of the NF-κB pathway did not suppress MARK4 expression. Thus, these results showed that SAHA attenuated IL-6 secretion in IL-1β-induced SMSCs through inhibition of the MARK4/NF-κB pathway.

滑膜来源的间充质干细胞 (SMSCs) 可以迁移到被破坏的髁状软骨部位并分化成软骨细胞以修复颞下颌关节 (TMJ) 损伤。白细胞介素 (IL)-1β 诱导的 IL-6 分泌已被证明可抑制 SMSC 的软骨形成潜力。组蛋白去乙酰化酶抑制剂辛二酰苯胺异羟肟酸 (SAHA) 最近已被证明与 IL-1β 诱导的炎症密切相关。然而，SMSCs 中 IL-1β 诱导的 SAHA 和 IL-6 分泌之间的关系仍不清楚。在这项研究中，我们评估了来自 TMD 患者和骨关节炎 (OA) 模型大鼠的滑膜标本中 IL-1β 和 IL-6 之间的关系。我们发现 IL-1β 和 IL-6 呈正相关，SMSCs 中 IL-6 的表达随着 IL-1β 刺激而增加体外。此外，微管亲和力调节激酶 4 (MARK4) 在 IL-1β 刺激的 SMSCs 和 OA 大鼠的滑膜中显着上调。MARK4 敲低抑制 IL-1β 刺激的 SMSCs 中的 IL-6 分泌和核因子 (NF)-κB 通路激活。SAHA 通过抑制 NF-κB 通路减弱 IL-1β 诱导的 SMSCs 中 IL-6 的分泌，并且 MARK4 在 SAHA 处理的 SMSCs 中也下调。然而，NF-κB 通路的抑制并没有抑制 MARK4 的表达。因此，这些结果表明，SAHA 通过抑制 MARK4/NF-κB 通路减弱了 IL-1β 诱导的 SMSCs 中 IL-6 的分泌。