MicroRNA-106b overexpression suppresses synovial inflammation and alleviates synovial damage in patients with rheumatoid arthritis

Abstract

Objectives To explore the effect of miR-106b on synovial inflammation and damage in rheumatoid arthritis (RA) patients, and further to investigate its possible mechanism. Methods : Quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, in situ hybridization and immunohistochemistry assay were separately used to verify the levels of miR-106b and cytokines in the synovial tissues of patients with RA or osteoarthritis (OA). Pearson correlation analysis was conducted to examine the bivariate relationship between miR-106b and cytokines or RANKL. Following the isolation and culture of fibroblast-like synoviocytes (FLS), the cells were transfected with lentivirus-mediated miR-106b mimic, miR-106b inhibitor, and negative control miR-106b mimic, respectively. Thereafter, cell proliferation was measured by Cell Counting Kit-8 assay, and cell invasion and migration capacity was assessed by Transwell assay. Furthermore, concentration and expression of cytokines were separately detected by Enzyme linked immunosorbent assay and Western blot. Results Compared with osteoarthritis, validation by qRT-PCR showed that RA patients had a lower level of miR-106b and higher levels of receptor activator of nuclear factor-κ B ligand (RANKL), tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6). Additionally, the scatter plot showed that the relative transcription of miR-106b level was negatively correlated to the level of TNF-a, IL-6, and RNKAL in the synovial tissues of both RA and OA patients (All P<0.05). Furthermore, miR-106b overexpression suppressed cell proliferation, migration and invasion capacity of human RA-FLS. Conclusions miR-106b overexpression suppresses synovial inflammation and alleviates synovial damage, thus it may be served as a potential therapeutic target for RA patients.

Comprehensive overview of microRNA function in rheumatoid arthritis

“…99 In addition, differential expression of both miR-9 and miR-106b in RA-FLSs leads to shifts not only in the invasive properties of RA-FLSs but also in RANKL levels, which affects osteoclastogenesis. 100,101 Decreased expression in RA-FLSs was also reported for miR-19, miR-20a, miR-27a, miR-29a, miR-152, miR192, miR-199a-3p, miR-375, miR-34a, miR-15a/16, and miR-3926. MiR-19a/b can act as a negative regulator of the inflammatory response in RA-FLSs, which is supported by evidence showing that miR-19a/b diminishes IL-6 and MMP-3 production via direct control of TLR2 expression.…”

Upregulation of Anti-Angiogenic miR-106b-3p Correlates Negatively with IGF-1 and Vascular Health Parameters in a Model of Subclinical Cardiovascular Disease: Study with Metformin Therapy

“…There is not currently unanimous agreement on the role of miR-106b-3p in cardiovascular pathology, but various studies show its involvement in mechanisms related to CVD. Studies have also associated its precursor miR-106b with suppression of cell proliferation [59] and angiogenesis [36].…”

Jianpi Qingre Tongluo Decoction exerted an anti-inflammatory effect on AS by inhibiting the NONHSAT227927.1/JAK2/STAT3 axis

“…Synovial hyperplasia and bone erosion are the characteristic features of many inflammatory joint disease including AS [ 4 ] Fibroblast-like synoviocytes (FLSs), a heterogenous cell population of the synovium, contribute actively to inflammatory responses and play a decisive role in the pathophysiological process of AS. FLSs secrete a variety of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) [ 5 ] and interleukin-6 (IL-6) to trigger and exacerbate inflammatory signaling cascades [ 6 , 7 ], leading to local inflammation and joint destruction [ 8 ]. At present, the main goals of AS management are to control inflammation, promote functional recovery, and reduce deformity [ 9 ].…”