**1. Introduction**

Rheumatoid arthritis (RA) is one of the most widespread inflammatory diseases that affect the immune system. The most common symptoms are pain, joint swelling, and disability. In RA occurs proliferative synovitis leading to bone and cartilage destruction. The inflamed synovium contains synovial fibroblasts, macrophages, and T cells that secrete inflammatory cytokines. They activate osteoclasts, causing bone destruction. In RA occurs undue immune response of T cells. CD4+ T cells contain helper T cells (Th cells) and they stimulate the immune responses as well as regulatory T cells (Treg cells) that control these responses. Th cells include Th1, Th2, and Th17 cells subsets. RA is characterized by an imbalance in Th17/Treg, and Th17 is more activated than Treg [1].

In osteoarthritis (OA), disease joint surfaces are damaged, resulting in a lack of maintaining joint cartilage homeostasis. Damages are caused by excessive mechanical stress like tensile strains and compression forces, trauma, or inflammation. It results in structural damage and deformation [2].

In recent times, microRNAs are considered as an essential player connected with the onset as well as the progression of osteoarthritis [1,3,4]. MicroRNAs (miRNAs, miRs) are single-stranded, conserved, noncoding RNAs, which have approximately 22 nucleotides in length. There has been a lot of interest in miRNAs research in recent years, and more than two thousand microRNAs have been discovered so far. It is becoming increasingly clear that miRNAs contribute to the number of biological processes, e.g., apoptosis and cell proliferation. MicroRNAs regulate gene expression post-transcriptionally. About one-third of the genes in the human genome is under the control of the miRNAs [5]. Apart from the repression of translation, miRNAs moreover begin the affinity and enrollment of mRNA restriction factors, which leads to degradation of mRNA and disrupts gene expression. MicroRNAs regulate both acquired and innate immunity by their contribution to the cytogenesis and generation of immune cells (e.g., dendritic cells, T cells, B cells). Altered miRNAs stimulate the production of undue autoantibodies and inflammatory cytokines secretion. The abovementioned processes lead to an imbalance of the immune system. As a result, miRNAs are linked with various autoimmune diseases. MiRNAs have a crucial role in the pathogenesis of diseases like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and primary biliary cholangitis (PBC) [4,5].

Yang et al. suggested that elevated miR-126 expression induces the hypomethylation of CD70 and CD11a genes, by the depression of DNMT1 protein, causing the onset and progression of RA [6]. Altered miR-24 occurs in RA and upregulation of this miRNA regulating the production of cytokines and causing deterioration of arthritis [7,8]. MiR-26a and miR-155 are linked to the immune responses and can suppress immune cell apoptosis; increase the activity of the immune system; and cause specific organ damage, including joint, skin, kidney, and lung [8]. Numerous microRNAs have been reported to be connected with synovial cell proliferation, osteoclast differentiation, and inflammatory cytokines and they have the potential to be used in the treatment of RA. MiR-155 and miR-146a are mentioned as representative miRNAs associated with the RA condition [2]. MiR-146a is critical for Treg cells suppressor function. The insufficiency of miR-146a in regulatory T cells caused a breach of immunological tolerance [9]. Suppressor of cytokine signaling 1 (SOCS1), the key negative controller of Janus kinase/Signal transducers and activators of transcription (JAK/STAT) signaling pathway [10], has been reported as the main target of miR-155 in peripheral blood mononuclear cells (PBMCs) of RA patients [2,11]. MiR-155 suppresses the expression of SOCS1 in activated CD4+ T cells and this leads to the stimulation of Interleukin-6/Signal transducer and activator of transcription 3 (IL-6/STAT3), and Interleukin-2/Signal transducer and activator of transcription 5 (IL-2/STAT5) signaling pathways, as well as the initiation of Treg/Th17 cells functions and differentiation [10].

Since microRNAs regulate gene expression of transcriptional factors, which impact Th17/Treg balance, assignment of the molecular mechanism of epigenetic as well as genetic regulation of Th17 and Treg cells is vital for comprehending RA etiology and pathogenesis. This study aimed to understand the potential influence of the selected microRNAs' expression profiles on the phenotype of RA. Moreover, we wanted to study and describe the regulation of five selected transcriptional factors, SOCS1, SMAD3, SMAD4, STAT3, and STAT5, by carefully chosen microRNAs in RA and control groups: OA and healthy control (HC). Moreover, we search for microRNAs that could be RA biomarkers.
