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透明质酸介导的细胞黏附分子通过增强成纤维样滑膜细胞的功能来诱导类风湿性关节炎的进展。

RHAMM induces progression of rheumatoid arthritis by enhancing the functions of fibroblast-like synoviocytes.

作者信息

Wu Jing, Qu Yuan, Zhang Yu-Ping, Deng Jia-Xin, Yu Qing-Hong

机构信息

Department of Rheumatology and Clinical Immunology, ZhuJiang Hospital, Southern Medical University, 253 Gongye Ave GuangZhou, GuangDong, 510282, China.

出版信息

BMC Musculoskelet Disord. 2018 Dec 26;19(1):455. doi: 10.1186/s12891-018-2370-6.

DOI:10.1186/s12891-018-2370-6
PMID:30587175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6307322/
Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune joint disease. Fibroblast-like synoviocytes (FLS) produce inflammatory cytokines and are involved in the migration and invasion of panuus tissue, which leads to the destruction of joints in RA. Receptor for hyaluronan mediated motility (RHAMM), is known to be one of the important receptors for hyaluronic acid. It has the ability to regulate migration of fibrocytes and infiltration of inflammatory cells. Here,we explored the mechanisms of RHAMM in RAFs.

METHODS

Quantitative PCR and western blot were performed to test the expression of RHAMM in synoviocytes of RA patients and osteoarthritis (OA) controls. Collagen antibody-induced arthritis (CAIA) was used to investigate the RHAMM expression in mouse synovial issues. RHAMM siRNA was used to detect the function of RHAMM in FLS.

RESULTS

RA-FLS has a significantly higher expression of RHAMM than OA-FLS. Expression of RHAMM in joint synovial tissue was markedly increased in the CAIA mice compared with the controls. RHAMM silencing using SiRNA was not only decreased the production of IL-6 and IL-8, but also inhibited the migration and invasion of RA-FLS.

CONCLUSIONS

RHAMM has an important role in the FLS induced modulation of inflammation and destruction of joints in RA.

摘要

背景

类风湿关节炎(RA)是一种慢性难治性自身免疫性关节疾病。成纤维样滑膜细胞(FLS)产生炎性细胞因子,并参与血管翳组织的迁移和侵袭,这导致了RA患者关节的破坏。透明质酸介导的运动受体(RHAMM)是已知的透明质酸重要受体之一。它具有调节纤维细胞迁移和炎性细胞浸润的能力。在此,我们探讨了RHAMM在类风湿关节炎成纤维样滑膜细胞(RAFs)中的作用机制。

方法

采用定量聚合酶链反应(PCR)和蛋白质免疫印迹法检测RA患者和骨关节炎(OA)对照滑膜细胞中RHAMM的表达。采用胶原抗体诱导的关节炎(CAIA)模型研究小鼠滑膜组织中RHAMM的表达。利用RHAMM小干扰RNA(siRNA)检测其在FLS中的功能。

结果

RA-FLS中RHAMM的表达明显高于OA-FLS。与对照组相比,CAIA小鼠关节滑膜组织中RHAMM的表达明显增加。使用siRNA沉默RHAMM不仅降低了白细胞介素(IL)-6和IL-8的产生,还抑制了RA-FLS的迁移和侵袭。

结论

RHAMM在FLS诱导的RA炎症和关节破坏调节中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/36b3cf8c8707/12891_2018_2370_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/e706af4cfa95/12891_2018_2370_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/de4a42b6d2a7/12891_2018_2370_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/0fd11419679f/12891_2018_2370_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/a29c866aa05f/12891_2018_2370_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/36b3cf8c8707/12891_2018_2370_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/e706af4cfa95/12891_2018_2370_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/de4a42b6d2a7/12891_2018_2370_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/0fd11419679f/12891_2018_2370_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/a29c866aa05f/12891_2018_2370_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed17/6307322/36b3cf8c8707/12891_2018_2370_Fig5_HTML.jpg

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