Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710038, PR China.
Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710038, PR China.
Biochem Biophys Res Commun. 2019 Jan 15;508(3):877-881. doi: 10.1016/j.bbrc.2018.12.030. Epub 2018 Dec 8.
A growing number of studies suggest that synovitis plays an important role in the pathogenesis and progression of osteoarthritis (OA). As a negative mediator of the nuclear factor-kappa B (NF-κB) signaling pathway, the zinc finger protein A20 has significant anti-inflammatory properties. In this study, the differential expression of A20 was investigated at the mRNA and protein levels in human normal OA fibroblast-like synoviocytes (FLSs) and normal FLSs pretreated with TNF-α. We then measured the activation of the NF-κB pathway and expression of pro-inflammatory cytokines in the above three groups by western blotting, a human cytokine array and ELISA. We found that TNF-α activated the NF-κB pathway, increased the expression of the pro-inflammatory cytokines IL-6 and IL-8, and A20 expression in human normal FLSs. However, the role of A20 in FLSs was unclear. To clarify this, we investigated the effect of A20 overexpression in human normal FLSs. The results indicate that A20 inhibits the NF-κB signaling pathway activation and OA-associated pro-inflammatory cytokines release. The results of this study indicate that A20 has anti-inflammatory effects in FLSs, which makes it a potential target for OA synovitis treatment.
越来越多的研究表明，滑膜炎在骨关节炎（OA）的发病机制和进展中起着重要作用。锌指蛋白 A20 作为核因子-κB（NF-κB）信号通路的负性调节剂，具有显著的抗炎特性。在这项研究中，我们在 mRNA 和蛋白水平上研究了 A20 在人正常 OA 成纤维样滑膜细胞（FLSs）和 TNF-α预处理的正常 FLSs 中的差异表达。然后，我们通过 Western blot、人细胞因子阵列和 ELISA 测量了上述三组细胞中 NF-κB 通路的激活和促炎细胞因子的表达。我们发现 TNF-α激活了 NF-κB 通路，增加了人正常 FLSs 中促炎细胞因子 IL-6 和 IL-8 的表达，同时也增加了 A20 的表达。然而，A20 在 FLSs 中的作用尚不清楚。为了阐明这一点，我们研究了 A20 过表达对人正常 FLSs 的影响。结果表明，A20 抑制了 NF-κB 信号通路的激活和 OA 相关的促炎细胞因子的释放。这项研究的结果表明，A20 在 FLSs 中具有抗炎作用，使其成为治疗 OA 滑膜炎的潜在靶点。
