Introduction
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and symmetric polyarthritis[1,2]. The principal pathological changes in RA include chronic persistent synovial inflammation, abnormal proliferation of synovial cells, extensive infiltration of inflammatory cells, formation of synovial membrane pannus, gradually eroded cartilage and subchondral bone, then resulting in destruction of joint tissue structure and loss of function[3,4]. RA has been reported to occured in people aged 40 to 60, while showing predominance in women more than men. Although current clinical treatment can alleviate some symptoms, it cannot reverse the damage caused to cartilage and related bone tissue, and the high disability rate of RA seriously affects the quality of patients life. The latest research have shown that the occurrence and development of RA is due to a combination of genetic, environmental and immune factors, but the specific mechanism is still unclear[5].
Fibroblast-like synoviocytes (FLS) are predominant component of joint synovial membrane[6], and plays an pivotal physiological role in controlling the volume of synovial fluid and maintaining the stability of joint cavity[7]. At the same time, FLS are also important factor leading to joint pathological damage[8]. During the occurrence and development of RA, FLS can occur three major abnormal changes: such as releasing large amounts of proinflammatory cytokines[9], FLS can promote the occurrence and maintenance of inflammatory response by involving in the activation of macrophages, T lymphocytes and NK cells[10]; such as dysplasia and apoptosis defect, both proliferation and invasion of FLS were significantly enhanced[11], exhibiting tumor-like behavior, accompanied by significant inhibition of apoptosis[12]; such as secreting matrix degrading enzymes, including matrix apoptosis-deficient metalloproteinases and cathepsin,leading to destruction of bone and cartilage[13,14]. A large number of studies have confirmed that abnormal proliferation and activation of FLS play a key role in the process of joint lesions in RA patients[15,16]. Therefore, inhibiting abnormal proliferation and activation of FLS may be a potentially therapeutic strategy to block or delay the progression of RA.
EBP50, also known as Na+/H+ exchange regulatory factor (NHERF1), is a PSD-95/Dlg-1, Drosophila disk large/ZO-1 (PDZ)-containing scaffolding protein that regulates a variety of physiological functions, such as controlling the localization, delivery, surface stability and function of transporters, integral membrane proteins, and ion channel proteins, as well as clustering of proteins to specific cellular domains to facilitate signaling. As a novel tumor suppressor gene. Previous studies have demonstrated that EBP50 expression was down-regulated in breast cancer[17], gastric cancer[18] and prostate cancer[19], and overexpression of EBP50 could effectively inhibit the proliferation of tumor cells and promote the apoptosis of tumor cells, at the same time, Related researchs also show that EBP50 can inhibit the migration and invasion of breast cancer cells by down-regulating MMPs and interacting with β-catenin[20,21].
However, most studies of EBP50 have focused on tumor cells, and it is not clear whether EBP50 can perform the same function in other cells. In this study, we investigated the effects and mechanisms of EBP50 overexpression on the Proliferation and Migration of Fibroblast-Like Synoviocytes in vitro.