miR-124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast-like synoviocytes via targeting PIK3/NF-κB pathway.

Abnormal hyperplasia of fibroblast-like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR-124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF-κB in RAFLS was examined by real-time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)-α and interleukin (IL)-6 was detected by ELISA. The joint swelling and inflammation in collagen-induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR-124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR-124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR-124a inhibited the expression of the key components of the PIK3/Akt/NF-κB signal pathway and inhibited the expression of pro-inflammatory factors TNF-α and IL-6. Local overexpression of miR-124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR-124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF-κB pathway. miR-124a is a promising therapeutic target for RA.

Yang B ，Ge Y ，Zhou Y ，Wang J ，Xie X ，Li S ，Tang M ，Xu L ，Tian J ... -  《-》

Down-regulation of microRNA-142-3p inhibits the aggressive phenotypes of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting nuclear factor-κB signaling.

The present study aimed to investigate the regulatory roles of miR-142-3p on the aggressive phenotypes of rheumatoid arthritis (RA) human fibroblast-like synoviocytes (RA-HFLSs), and reveal the potential mechanisms relating with nuclear factor-κB (NF-κB) signaling. miR-142-3p expression was detected in RA synovial tissues and RA-HFLSs by quantitative real-time PCR (qRT-PCR) and Northern blot analysis. RA-HFLSs were transfected with miR-142-3p inhibitor and/or treated with 10 µg/l tumor necrosis factor α (TNF-α). The viability, colony formation, apoptosis, migration, invasion, and the levels of interleukin (IL)-6, and matrix metalloproteinase 3 (MMP-3) were detected. The mRNA expressions of B-cell lymphoma-2 (Bcl-2), Bax, Bad, IL-6, and MMP-3 were detected by qRT-PCR. Moreover, the expression of Bcl-2, IL-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blot. The interaction between IRAK1 and miR-142-3p was identified by dual luciferase reporter gene assay. MiR-142-3p was up-regulated in RA synovial tissues and RA-HFLSs. TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs. MiR-142-3p inhibitor significantly reversed TNF-α-induced up-regulation of IRAK1, TLR4, and p-NF-κB p65 in TNF-α-treated RA-HFLSs. Besides, IRAK1 was a target of miR-142-3p. The down-regulation of miR-142-3p inhibited the aggressive phenotypes of RA-HFLSs through inhibiting NF-κB signaling.

Qiang J ，Lv T ，Wu Z ，Yang X ... -  《-》

Up-regulated microRNA-411 or declined RIPK1 inhibits proliferation and promotes apoptosis of synoviocytes in rheumatoid arthritis mice via decreased NF-κB pathway.

Huang Y ，Chen K ，Yu H ，Chen D ，Deng L ，Zhang Y ，Xue X ，Pan X ... -  《-》

MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis.

Chen Y ，Xian PF ，Yang L ，Wang SX ... -  《-》

Kaempferitrin inhibits proliferation, induces apoptosis, and ameliorates inflammation in human rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a complex chronic inflammatory disease that is associated with the aberrant activation of fibroblast-like synoviocytes (FLS). Kaempferitrin is a natural flavonoid glycoside that possesses anti-inflammatory bioactivity. However, the effect of kaempferitrin on RA has not yet been revealed. The aim of the present study was to investigate the effect of kaempferitrin on human RA-FLS MH7A cell line. We found that kaempferitrin inhibited proliferation and induced apoptosis of MH7A cells. Kaempferitrin decreased the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-1, and MMP-3 in MH7A cells. Moreover, kaempferitrin blocked the activation of nuclear factor-κB (NF-κB) and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways. Furthermore, treatment with kaempferitrin decreased paw thickness and arthritis scores, and reduced the serum levels of IL-1β, IL-6, and TNF-α in a collagen-induced arthritis mouse model. In conclusion, kaempferitrin inhibited cell proliferation, induced cell apoptosis, and ameliorated inflammation of RA-FLS by suppressing the NF-κB and Akt/mTOR pathways.

Wang J ，Zhao Q 《-》