Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

• Published in: Scientific reports 2017-10, Vol.7 (1), p.12671-13, Article 12671
• Main Authors: Li, Xiao-Feng, Sun, Ying-Yin, Bao, Jing, Chen, Xin, Li, Yu-Huan, Yang, Yang, Zhang, Lei, Huang, Cheng, Wu, Bao-Ming, Meng, Xiao-Ming, Li, Jun
• Format: Article
• Language: English
• Subjects: 13/21; 631/250; 692/4017; 82/51; Animals; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Autoimmune diseases; c-Myc protein; Cell Movement; Cell Proliferation; Cyclin D1; Down-Regulation; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Gelatinase B; Humanities and Social Sciences; Interstitial collagenase; Matrix metalloproteinase; multidisciplinary; Myc protein; Osteoarthritis; Peroxisome proliferator-activated receptors; PPAR gamma - agonists; PPAR gamma - metabolism; Rats, Sprague-Dawley; Rheumatoid arthritis; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Signal transduction; siRNA; Synoviocytes; Synoviocytes - metabolism; Synoviocytes - pathology; Synovium; Tissue inhibitor of metalloproteinase 1; Wnt protein; Wnt Signaling Pathway; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-12570-6

Peroxisome proliferator-activated receptor (PPAR)-γ is involved in both normal physiological processes and pathology of various diseases. The purpose of this study was to explore the function and underlying mechanisms of PPAR-γ in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) proliferation and migration. In the present study, we found PPAR-γ expression was remarkably reduced in RA synovium patient compare with OA and normal, as well as it was low-expression in Adjuvant-induced arthritis (AA). Moreover, inhibition PPAR-γ expression by T0070907 (12.5 μM) or PPAR-γ siRNA could promote FLSs proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, except for TIPM-1. These date indicate that up-regulation of PPAR-γ may play a critical role in RA FLSs. Interestingly, co-incubation FLSs with Pioditazone (25 μM) and over expression vector with pEGFP-N1-PPAR-γ reduced proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, besides TIMP-1. Further study indicates that PPAR-γ may induce activation Wnt/β-catenin signaling. In short, these results indicate that PPAR-γ may play a pivotal role during FLSs activation and activation of Wnt/β-catenin signaling pathway.