Research Article: Modulation of platelet-derived microparticles to adhesion and motility of human rheumatoid arthritis fibroblast-like synoviocytes

Date Published: July 13, 2017

Publisher: Public Library of Science

Author(s): Wenwen Wang, Jiahuan Liu, Binzhou Yang, Zhongshuang Ma, Guiping Liu, Weigan Shen, Yu Zhang, Jung Weon Lee.

http://doi.org/10.1371/journal.pone.0181003

Abstract

Platelet-derived microparticles (PMPs) are closely associated with disease activity in rheumatoid arthritis (RA) and contribute to the inflammatory process. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play important roles in the progression of joint destruction. The aim of this study is to demonstrate whether PMPs affect the adhesion and motility of RA-FLSs. Our data indicated that PMPs promoted migration, invasion and adhesion to extracellular matrix (ECM) of RA-FLSs. Further study showed that PMPs up-regulated the expression of matrix metalloproteinase-1 (MMP1) and increased the level of phosphorylation of NF-κB (p-NF-κB) and Erk (p-Erk) in RA-FLSs. These results suggest that PMPs promote RA-FLSs adhesion and motility presumably by increasing MMP1 via activating Erk-mediated NF-κB pathway.

Partial Text

Rheumatoid arthritis (RA), a chronic autoimmune disease, is characterized by synovial hyperplasia, inflammatory cells infiltration and pannus formation, which erode cartilage and bone, ultimately trigger joint destruction and functional disability [1]. Although detailed pathogenesis of RA remains unclear, accumulating evidences suggest that rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play a crucial role in the pathogenesis of RA [2,3]. It have been reported that activated RA-FLSs predominantly located in synovial intimal lining manifest features such as abnormal proliferation, apoptosis resistance, as well as invasion to adjacent tissues [4,5], and RA-FLSs not only secrete a variety of inflammatory cytokines and chemokines that are responsible for the synovial inflammation processes, but also release some matrix degrading enzymes such as matrix metalloproteinases (MMPs) that aggravate cartilage and bone damage [6–8]. Considering RA-FLSs are able to migrate and invade to normal tissues and accelerate the development of the disease [9,10], inhibition of motility of RA-FLSs might be considered as a potential target for novel treatment strategies for RA.

Accumulating evidences showed that activation of platelet play a crucial role in many autoimmune diseases, such as RA, systemic lupus erythematosus and ankylosing spondylitis, and the process in platelet activation was accompanied by the formation of PMPs, which amplify the inflammatory reaction of autoimmune disease as a kind of inflammatory body [13,22,23]. In addition, it have been documented that the levels of PMPs both increased in peripheral blood and synovial fluid of RA patients [15], and PMPs might be associated with disease activity of RA and involved in the pathogenesis of RA. In the present study, we revealed that PMPs play a positive role in regulation of adhesion and motility of RA-FLSs presumably through Erk activating NF-κB signaling.

 

Source:

http://doi.org/10.1371/journal.pone.0181003

 

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