Suberoylanilide Hydroxamic Acid Attenuates Interleukin-1β-Induced Interleukin-6 Upregulation by Inhibiting the Microtubule Affinity-Regulating Kinase 4/Nuclear Factor-κB Pathway in Synovium-Derived Mesenchymal Stem Cells from the Temporomandibular Joint

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)-1 beta-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-1 beta. However, the relationship between SAHA and IL-6 secretion induced by IL-1 beta in SMSCs remains unclear. In this study, we evaluated the relationships between IL-1 beta and IL-6 in synovial specimens from patients with TMD and in model rats with osteoarthritis (OA). We found that IL-1 beta and IL-6 were positively correlated and that IL-6 expression in SMSCs increased with IL-1 beta stimulation in vitro. Moreover, microtubule affinity-regulating kinase 4 (MARK4) was significantly upregulated in IL-1 beta-stimulated SMSCs and in the synovium of rats with OA. MARK4 knockdown inhibited IL-6 secretion and nuclear factor (NF)-kappa B pathway activation in IL-1 beta-stimulated SMSCs. SAHA attenuated IL-6 secretion in IL-1 beta-induced SMSCs through NF-kappa B pathway inhibition, and MARK4 was also downregulated in SAHA-treated SMSCs. However, inhibition of the NF-kappa B pathway did not suppress MARK4 expression. Thus, these results showed that SAHA attenuated IL-6 secretion in IL-1 beta-induced SMSCs through inhibition of the MARK4/NF-kappa B pathway.