Abstract
BackgroundAs a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation. More recently, long non-coding RNAs (lncRNAs) have been implicated in the progression of various diseases including the progression of RA. Hence, the aim of the current study was to investigate the role by which the lncRNA, plasmacytoma variant translocation 1 (PVT1), influences RA-FLSs and its ability to modulate the methylation of sirtuin 6 (sirt6).MethodsRA rat models were initially established to determine the expression of PVT1 and sirt6 in synovial tissues and RA-FLSs. Elevation or depletion of PVT1 or sirt6 was achieved by means of transformation with plasmids in order to investigate their effects on RA-FLS proliferation, inflammation and apoptosis. The localization of PVT1 and its binding ability to the sirt6 promoter region were also explored in an attempt to elucidate the correlation between PVT1 and sirt6 methylation.ResultsHigh expression of PVT1 and low expression of sirt6 were detected in the synovial tissues and RA-FLSs of the rat models. RA-FLSs treated with sh-PVT1 or oe-sirt6 exhibited suppressed cell proliferation, inflammation and induced apoptosis. PVT1 was predominately localized in the nucleus while evidence was obtained indicating that it could bind to the sirt6 promoter to induce sirt6 methylation, thus inhibiting sirt6 transcription. PVT1 knockdown was observed to restore sirt6 expression through decreasing sirt6 methylation, thereby alleviating RA.ConclusionThe key findings of the study provide evidence suggesting that, PVT1 knockdown is able to restrain RA progression by inhibiting sirt6 methylation to restore its expression.
Highlights
As a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation
We concluded that the success rate of RA rat model was 80%
We aimed to investigate the functional roles of plasmacytoma variant translocation 1 (PVT1) in RA-FLS in an attempt to further elucidate the finer mechanisms associated with the pathogenesis of RA
Summary
As a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation. Rheumatoid arthritis (RA) represents a type of autoimmune joint inflammatory disorder and has been reported to affect approximately 6% of people over 65 years old, while showing predominance in women more so than men [1]. The disease is often accompanied by invasiveness of macrophages, synovial fibroblasts (SFs), T lymphocytes, and B lymphocytes/ plasma cells, which results in the perpetuation of joint destruction in RA, which if left untreated, often leads to disability, decrease in quality of life as well as elevated comorbidity [3]. RA fibroblast-like synoviocytes (RA-FLSs) are predominant component that have been implicated in the initiation, progression and perpetuation of joint destruction inflammation. Improved knowledge of inflammation in RA will help to understand disease pathogenesis, which can be eventually used for RA treatments and/or preventions
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