BackgroundLong non-coding RNAs (lncRNAs) have drawn increasing attention because they play a pivotal role in various types of autoimmune diseases, including rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs), a prominent component of hyperplastic synovial pannus tissue, are the primary effector cells in RA synovial hyperplasia and invasion which can lead to joint destruction. In this study, we investigated whether lncRNAs could act as competing endogenous RNAs to regulate the pathological behaviors of RA-FLSs.MethodsLncRNA microarray was conducted to establish lncRNA expression profiles in FLSs isolated from RA patients and healthy controls (HCs). Differentially expressed lncRNAs were verified by quantitative real-time PCR (qRT-PCR) on RA-FLSs and synovial fluid. The functional role of lncRNA PICSAR downregulation was evaluated in RA-FLSs. We conducted molecular biological analysis to predict miRNAs which have a potential binding site for PICSAR and further refined the results by qRT-PCR. Luciferase reporter assay was adopted to validate the interaction of lncRNA PICSAR and miR-4701-5p. Western Blot and qPCR were used to identify the target gene and protein. The functional role of miR-4701-5p upregulation was examined in RA-FLSs.FindingsWe identified a long intergenic non-protein-coding RNA162 (LINC00162), also known as lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA), has significantly higher expression in RA-FLSs and RA synovial fluid. The cell proliferation, migration, invasion and proinflammatory cytokines production of RA-FLSs showed significant alterations after the lncRNA PICSAR suppression. Mechanistically, lncRNA PICSAR functioned through sponging miR-4701-5p in RA-FLSs.InterpretationOur results reveal PICSAR may exert an essential role in promoting synovial invasion and joint destruction by sponging miR-4701-5p in RA and that lncRNA PICSAR may act as a biomarker of RA.

BackgroundEvidence to support Mesenchymal stem cells (MSCs) treatment in Sjögren's syndrome (SS) has been verified. This study aims to evaluate the effectiveness of heterogeneous MSCs therapies, identify optimal experimental parameters and explore possible underlying mechanisms in animal models of SS.MethodsLiterature searches were performed in PubMed, Web of Science and EMBASE. Effect sizes of SS treatments with MSCs were extracted and analyzed by two authors independently.ResultsA total of 13 studies and 20 treatment arms met the inclusion criteria. When compared with the controls, MSCs treatment resulted in lower level of histological score (SMD= -2.208; 95%CI= -3.129, -1.286; P<0.001) accompanied by an improved trend of salivary flow rate (SFR) (SMD = 1.726; 95%CI= 1.340, 2.113; P <0.001) and Schirmer's test results (SMD= 3.379; 95% CI= 2.141, 4.618; P<0.001). In MSCs groups, levels of autoantibodies decreased to varying degrees. Treg cells were increased and Th17 cells were decreased in both lymph nodes and spleens. Additionally, IL-6 reduction and IL-10 elevation were found in local lesional tissues. Furthermore, TNF-α level dropped either in sera or glands. Notably, the cell injection frequency and routes may be two important factors affecting the effect of MSCs therapy.ConclusionTo the best of our knowledge, this is the first meta-analysis to quantitatively evaluate MSCs therapeutic effects on SS. Our research emphasizes optimizing MSC treatment strategies to achieve better outcomes, thereby providing a valuable reference for clinical application.