| Backgrounds:Rheumatoid arthritis (RA) is an autoimmune disease which mainlyimpaired peripheral joints. Pathological characteristics of RA areinflammatory cells infiltrated into synovial tissue, tumor like proliferation ofsynovial tissue and pannus which damaged the cartilage and sclerotin.Erythropoietin receptor (EpoR), firstly found in the erythroid colonyforming unit, combined with Epo to adjust the hyperplasia of erythroid andthe maturity of reticulocyte. Researches in recent years suggest that EpoRplays an important role in tumor growth, as several tumor tissues and cells canexpress EpoR and Epo closely related to pathological processes such as tumorcells proliferation and resistance to apoptosis have been verified byconsiderable researches. In addition, currently, researchers considered thatEpo can be induced to express in endothelial cells by hypoxia, and throughexperiment confirmed that Epo can promote the angiogenesis obviously.Epo/EpoR signal pathway plays a vital role in promoting tumor vasculargrowth, tumor infiltration, tumor resistance to apoptosis, and so on, and themain pathological change of RA synovial pannus is angiogenesis andfibroblast like synoviocytes (FLS) which is characteristiced with a feature oftumor like proliferation for growth. So we aimed to explore whether EpoRparticipated in the pathogenesis of RA through detecting the expression ofEpoR in the synovial tissue, plasma and synovial fluid, and to preliminarilyanalyze the correlation of EpoR with synovial angiogenesis and synovial cells growth from RA patients.Objectives:1. Through detecting EpoR level in synovial and plasma from RApatients, and the synovial and plasma level of OA patients and plasma ofhealthy cases as a control with ELISA, in order to analyze and explore thesignificance of EpoR in RA.2. To investigate the expression of EpoR level in synovial tissue of RAand OA patients by immunohistochemistry, and analyze its expression sitesand role in synovial tissue preliminarily.3. To explore the effect of recombinant human erythropoietin (rhEpo) onsynovial cells growth in RA patients.Methods:1. The level of EpoR from 43 RA patients with synovia samples and 34with plasma were detected, 16 OA with synovia and 32 healthy volunteers or22 OA patients with plasma as controls.2. The EpoR in synovium tissues was detected by immunohistochemistryin 13 RA and 9 OA patients. Further to explore the role of EpoR in RApathogenesis.3. FLS of RA were separated and cultured in vitro. The MTT methodswere applied to analysis the proliferation of FLS treated with rhEpo.Results:1. The level of EpoR (84.95+11.29 ng/ml ) in RA synovia was obviouslyhigher than those in RA plasma(69.78+8.15 ng/ml), synovia(71.82+9.92 ng/m)or plasma(68.89+8.77 ng/ml) level in OA patients and plasmalevel(66.59+10.61 ng/ml) in healthy controls. There is no significantdifference between plasma level of RA and OA patients or healthy controls. 2. The synovia EpoR level in RA was correlation with ESR(r=0.35p<0.05) and CRP (r=0.31 p<0.05), but it had no association with swollencounts, tender joint counts and disease activity score 28.3. The positive prevalence of EpoR in RA synovium was obviouslyhigher than those in OA synovium. It mainly localized in vascular endothelialcells and FLS.4. Applying different concentrations of rhEpo to stimulate FLS, wefound the concentration of 50U/ml had a highest OD value in MTT test.When the EpoR concentration was 50U/ml, the proliferation of FLS washigher than control groups at 24h or 48h(p<0.05, p<0.001).Conclusions:1. The EpoR level in synovial fluid of RA patients is higher, and isassociated with inflammatory factors, which may suggest a relationshipbetween EpoR expression and inflammatory process of RA.2. The positive rate of EpoR expression in RA synovial tissue is higherthan in OA, and gives priority to vascular endothelial cells and FLS cells.3. EpoR may involve in the proliferation of pannus in damaged joints ofRA patients.4. The rhEpo may improve FLS cells proliferation in RA patients. |
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