HDAC10 upregulation contributes to interleukin 1β-mediated inflammatory activation of synovium-derived mesenchymal stem cells in temporomandibular joint

Abstract

Histone deacetylases (HDACs) are important in chronic inflammation, and inflammatory responses affect synovium-derived mesenchymal stem cell (SMSC) function in temporomandibular joint repair. However, the effect of HDACs on SMSC inflammatory activation remains unclear. In this study, temporomandibular joint fibroblast-like synoviocytes obtained from osteoarthritis patients met the minimal mesenchymal stem cell criteria. Interleukin 1β (IL-1β) upregulated IL-6 and IL-8 expression in SMSCs through nuclear factor-κB (NF-κB) pathway activation. IL-6 and IL-8 upregulation were blocked by broad-acting HDAC inhibitors SAHA and LBH589. MC1568 alleviated IL-1β activation of SMSCs, whereas CI994 and FK228 produced a minimal or opposite effect in vitro. We also found HDAC10 was highly associated with localized IL-1β expression in vivo and in vitro. HDAC10 knockdown alleviated IL-1β-mediated SMSC activation and blocked NF-κB pathway activation. Conversely, HDAC10 overexpression promoted IL-6 and IL-8 expression and IL-1β-mediated NF-κB pathway activation. In conclusion, HDAC10 upregulation contributed to IL-1β-mediated inflammatory activation of SMSCs, indicating that HDAC10 may be a novel therapeutic target.

Keywords: NF-κB signaling pathway; histone deacetylase; inflammation; synovium-derived mesenchymal stem cell; temporomandibular joint disorders.