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.