Abstract
Background: Rheumatoid arthritis (RA) patients mainly suffer from pain, which is associated with inflammation, peripheral and central pain processing, and joint structure damage. Tripterygium glycosides (TG) could significantly reduce joint pain and swelling in RA in clinic. The aim of the study is to explore the intervention mechanism of TG treating RA pain through regulating the key miRNA and its target genes. Methods: Collagen-induced arthritis(CIA) was induced in DBA/1 mice. TG was administrated by intragstric everyday for four weeks. The paw swelling, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), TNF-a and PGE2 levels in sera were investigated. MiR-143-3p expression in blood and DRG were detected. MiR-143 target genes were predicted. DRG cells were cultured and transfected with miR-143-3p inhibitor or mimics, and the expressions of miR-143-3p, Mrgpre, Ptgs2, Tnf, Ptgdr were observed. Meanwhile, Mrgpre, Ptgs2 and Tnf expressions in DRG of mice were also investigated. Results: Compared with CIA model group, TG had notable effects on reliving paw swelling, arthritis score and elevation in MWT and TWL, decreasing the levels of TNF-a and PGE2 in sera, and inhibiting the histological damage. Low miR-143-3p expressions in blood and DRG tissue were found in CIA mice, and TG could increase the expression of miR-143-3p. Ptgs2, Mrgpre, Ptgdr and Tnf were selected as target genes of miR-143. The expressions of Mrgpre, Ptgs2 and Tnf were significantly inhibited after transfected with miR-143-3p mimics, while increased after inhibitor tranfection. The results indicated that miR-143 expression was negatively correlated with those target genes of Mrgpre, Ptgs2 and Tnf. Meanwhile, the expressions of Ptgs2, Mrgpre and Tnf in DRG of CIA mice were significantly up-regulated, and TG could inhibit the expressions of Mrgpre, Ptgs2 and Tnf. Conclusion: CIA mice exhibit significant hyperalgesia and high levels of inflammatory pain mediators. MiR-143-3p plays an important role in regulating chronic inflammatory pain and neuropathic pain through negatively modulating Mrgpre, Ptgs2 and Tnf expressions. TG inhibits the pain responses in RA through regulating miR-143-3p and its related target genes.
