HDAC10 upregulation contributes to interleukin 1-mediated inflammatory activation of synovium-derived mesenchymal stem cells in temporomandibular joint
HDAC10 upregulation contributes to interleukin 1-mediated inflammatory activation of synovium-derived mesenchymal stem cells in temporomandibular joint
复制标题
HDAC10上调有助于白细胞介素1介导的颞下颌关节滑膜间充质干细胞的炎症激活
DOI：
10.1002/jcp.27873
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Sun, Yangpeng
中科院分区：
文献类型：
--
作者：
Liao, Wenting;Sun, Jiadong;Sun, Yangpeng
组蛋白去乙酰化酶（HDAC）在慢性炎症中起重要作用，炎症反应影响滑膜间充质干细胞（SMSC）在颞下颌关节修复中的功能。然而，HDAC对SMSC炎性活化的影响仍不清楚。在这项研究中，从骨关节炎患者中获得的颞下颌关节成纤维细胞样滑膜细胞符合最小间充质干细胞标准。白细胞介素1（IL-1）通过核因子-B（NF-B）途径上调SMSCs中IL-6和IL-8的表达。IL-6和IL-8上调被广泛作用的HDAC抑制剂SAHA和LBH 589阻断。MC 1568减轻SMSCs的IL-1活化，而CI 994和FK 228在体外产生最小或相反的作用。我们还发现HDAC 10与体内和体外局部IL-1表达高度相关。HDAC 10敲低可减轻IL-1介导的SMSC活化并阻断NF-B途径活化。相反，HDAC 10过表达促进IL-6和IL-8表达以及IL-1介导的NF-B通路活化。总之，HDAC 10上调有助于IL-1介导的SMSCs炎症激活，表明HDAC 10可能是一种新的治疗靶点。
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 1 (IL-1) upregulated IL-6 and IL-8 expression in SMSCs through nuclear factor-B (NF-B) pathway activation. IL-6 and IL-8 upregulation were blocked by broad-acting HDAC inhibitors SAHA and LBH589. MC1568 alleviated IL-1 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-1 expression in vivo and in vitro. HDAC10 knockdown alleviated IL-1-mediated SMSC activation and blocked NF-B pathway activation. Conversely, HDAC10 overexpression promoted IL-6 and IL-8 expression and IL-1-mediated NF-B pathway activation. In conclusion, HDAC10 upregulation contributed to IL-1-mediated inflammatory activation of SMSCs, indicating that HDAC10 may be a novel therapeutic target.