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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.

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.