HMGB1-LPS complex promotes transformation of osteoarthritis synovial fibroblasts to a rheumatoid arthritis synovial fibroblast-like phenotype.
HMGB1-LPS complex promotes transformation of osteoarthritis synovial fibroblasts to a rheumatoid arthritis synovial fibroblast-like phenotype.
复制标题
HMGB1-LPS 复合物促进骨关节炎滑膜成纤维细胞向类风湿关节炎滑膜成纤维细胞样表型的转化。
DOI：
10.1038/cddis.2014.48
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发表时间：
2014-02-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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作者：
一般认为，某些炎性抗原可识别滑膜成纤维细胞（SF）上的Toll样受体，激活下游信号，导致RASF的形成，诱发类风湿关节炎（RA）。本工作的目的是研究外部PAMP（LPS）与内部DAMP（HMGB 1）结合形成复合物，识别SFs上的TLR/TLR，从而启动信号级联反应，导致炎性细胞因子和趋化因子的分泌、组织破坏酶的产生和RASFs的形成，最终导致RA的发生。将人骨关节炎滑膜成纤维细胞（OASFs）与HMGB 1-LPS复合物共培养5代，诱导OASFs向RA样SFs（tOASFs）转化。然后，在体外研究了tOASFs在细胞周期和凋亡-自噬平衡中的变化，并在SCID小鼠模型中评价了tOASFs的体内致病性。体外细胞周期分析显示更多的tOASFs通过G1/S检查点并进入S或G2期。流式细胞术和共聚焦显微镜显示，与OASFs相比，tOASFs中凋亡减少，自噬增强。tOASFs中某些受体和粘附分子的表达上调。体内实验表明，tOASFs附着，入侵，并降解共植入软骨。此外，组织化学显示tOASFs过度增殖和基质金属蛋白酶（MMPs）的表达。以上结果表明，HMGB 1-LPS复合物可促进RASFs的形成。
It is generally believed that some inflammatory antigens can recognize Toll-like receptors on synovial fibroblasts (SFs) and then activate downstream signals, leading to the formation of RASFs and inducing rheumatoid arthritis (RA). The objective of the current work was to study on the hypothesis that outer PAMP (LPS) binds to the inner DAMP (HMGB1) and becomes a complex that recognizes TLRs/RAGE on SFs, thus initiating a signaling cascade that leads to the secretion of inflammatory cytokines and chemokines, production of tissue-destructive enzymes, and formation of RASFs, finally resulting in RA. Osteoarthritis synovial fibroblasts (OASFs) were co-cultured with HMGB1–LPS complex in vitro for five generations to induce the transformation of human SFs to RA-like SFs (tOASFs). Then, changes of tOASFs in cell cycle and apoptosis–autophagy balance were investigated in vitro, and the pathogenicity of tOASFs was evaluated in a SCID mouse model in vivo. In vitro cell cycle analysis showed more tOASFs passing through the G1/S checkpoint and moving to S or G2 phase. Flow cytometry and confocal microscopy showed that apoptosis was reduced and autophagy was enhanced significantly in tOASFs as compared with those in OASFs. The expression of certain receptors and adhesion molecules in tOASFs was upregulated. In vivo experiments showed that tOASFs attached to, invaded, and degraded the co-implanted cartilage. In addition, histochemistry showed excessive proliferation of tOASFs and the expression of matrix metalloproteinases (MMPs). Based on the above findings, we conclude that HMGB1–LPS complex could promote the formation of RASFs.
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影响因子：
5.1
作者：
通讯作者：
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HMGB1和脐带血：其在先天免疫中作为免疫辅助因素的作用。
影响因子：
3.7
作者：
Ciucci A;Gabriele I;Percario ZA;Affabris E;Colizzi V;Mancino G
通讯作者：
Mancino G
影响因子：
--
作者：
JOHNSON, BA;HAINES, GK;KOCH, AE
通讯作者：
KOCH, AE
影响因子：
4.9
作者：
Andreas, Kristin;Luebke, Carsten;Sittinger, Michael
通讯作者：
Sittinger, Michael
影响因子：
4.7
作者：
Gong, Quan;Zhang, Hui;Gong, Fei-li
通讯作者：
Gong, Fei-li