HMGB1 contributes to osteoarthritis of temporomandibular joint by inducing synovial angiogenesis
HMGB1 contributes to osteoarthritis of temporomandibular joint by inducing synovial angiogenesis
复制标题
HMGB1通过诱导滑膜血管生成导致颞下颌关节骨关节炎
DOI：
10.1111/joor.13129
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发表时间：
2020-12-09
影响因子：
2.9
通讯作者：
Long, Xing
中科院分区：
文献类型：
--
作者：
Feng, Yaping;Hu, Shiyu;Long, Xing
研究背景高迁移率族蛋白1（HMGB 1）与炎症反应有关.本研究旨在探讨高迁移率族蛋白B1（HMGB 1）是否促进颞下颌关节骨关节炎（TMJOA）滑膜血管生成及其机制。血管内皮生长因子（VEGF）和缺氧诱导转录因子-1 α的表达通过Western blotting、实时荧光定量PCR和免疫荧光染色检测细胞中HIF-1 α的表达。通过人脐静脉内皮细胞（HUVECs）的管形成和细胞迁移来测定这些细胞的血管生成能力。分别加入HMGB 1、VEGF、Erk或JNK特异性抑制剂。制备完全弗氏佐剂（CFA）诱导的TMJOA大鼠。结果HMGB 1通过激活Erk和JNK，有效上调TMJOA滑膜成纤维细胞VEGF和HIF-1 α的表达。HMGB 1处理的TMJOA滑膜成纤维细胞的条件培养基显着促进HUVECs的管形成和迁移，而加入某些VEGF抑制剂后则减弱。此外，针对HMGB 1的特异性抑制剂消除了CFA注射诱导的大鼠TMJOA滑膜中的新血管形成和HIF-1 α、VEGF和CD 34的产生。此外，这种抑制剂导致IL-6，IL-1 β和TNF-α的减少，在这些rats.Conclusion这些研究结果揭示了一个关键的作用，HMGB 1在管理滑膜血管生成和作为一个治疗靶点对TMJOA。
Background High- mobility group 1 protein (HMGB1) is related with inflammation. Our former research reported that substantial HMGB1 situates at the synovium of osteoarthritis of temporomandibular joint (TMJOA) patients.Objective This study investigated whether HMGB1 promotes synovial angiogenesis of TMJOA and its underlying mechanism.Methods Human synovial fibroblasts were stimulated with HMGB1; the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha) in these cells was explored by Western blotting, real-time PCR and immunofluorescent staining. The angiogenic capacity of these cells was assayed by tube formation and cell migration of human umbilical vein endothelial cells (HUVECs). The specific inhibitor against HMGB1, VEGF, Erk or JNK was added in these cells, respectively. Complete Freund's adjuvant (CFA)-induced TMJOA rats were produced. The changes in their synovium and synovial fluid were detected by immunofluorescent staining and ELISA.Results HMGB1 effectively up-regulated the production of VEGF and HIF-1 alpha in TMJOA synovial fibroblasts through the activation of Erk and JNK. Conditioned medium from HMGB1-treated TMJOA synovial fibroblasts significantly promoted tube formation and migration in HUVECs, while attenuated those after the addition of certain inhibitor for VEGF. Furthermore, the specific inhibitor against HMGB1 vanished the neovascularisation and production of HIF-1 alpha, VEGF and CD34 in the synovium of rat TMJOA induced by CFA injection. Additionally, this inhibitor led to the reduction of IL-6, IL-1 beta and TNF-alpha in the synovial fluid of those rats.Conclusion These findings disclose a key role for HMGB1 in governing synovial angiogenesis and as a therapeutic target against TMJOA.