| Objectives: Growing evidence suggests that adipokines, especially adiponectin (AD), the most abundant adipokines in serum, play an important role in regulation of immunization and inflammation contributed to the pathogenesis of rheumatoid arthritis (RA). We previously reported that adiponectin was higher expressed in synovial fluids of RA than Osteroarthritis (OA). Interestingly, data from our microarray analysis showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a novel adipokine, was high expressed in the peripheral blood mononuclear cell (PBMC) of another inflammatory arthritis spondyloarthritis. The purpose to this study is to investigate the role of AD and HB-EGF in chronic inflammation and osteoclasia of RA.Methods: (1) Plasma and PBMC samples collected from the 62 RA patients. Age, sex and BMI matched 22 healthy individuals were as controls (HC) . The serum levels of AD and HB-EGF were assayed by ELISA kit. The expression of AD and HB-EGF mRNA in PBMC were detected by real-time PCR. (2) ELISA was used to determine the levels of AD, IL-1β, IL-6 and TNF-αin synovial fluids in RA and OA. (3) The expression of RANKL was detected by real-time PCR after MH7A treated with AD, IL-6 or both AD and IL-6. (4) To construct the type 2 recombinant adeno-associated virus vector encoding the gene of AD (rAAV2-adiponectin). THP-1 was transduced by rAAV2-adiponectin virus. The expression of AD were detected by RT-PCR, and the expression of IL-1β, IL-6 and TNF-α, were detected by real-time PCR after 7d. Results: (1) When stratifying RA patients into high active group and moderate or low active group based on DAS28 score, the high active group (15.8±2.7 ug/ml,745.9±217.0pg/ml)displayed higher levels of serum AD and HB-EGF than the moderate(13.8±2.6 ug/ml,715.8±189.3pg/ml), low (14.9±1.4 ug/ml,575.4±75.1 pg/ml)or remission active subgroup(13.4±2.1 ug/ml, 561.5±80.5 pg/ml) and HC (13.5±2.1 ug/ml, 492.2±59.9 pg/ml)(p <0.05, respectively). Correlation coefficient analysis indicated that serum AD and HB-EGF levels were significant positive correlation with RA clinical parameter of ESR, CRP or RF (r =0.3-0.5, P<0.01, respectively). No significant difference in HB-EGF mRNA in PBMC was observed between RA subgroup and HC. The mRNA expression of AD was not detected in PBMC in each group. (2) Higher levels of AD, IL-1β, IL-6 and TNF-αwere detected in RA synovial fluids than in OA. High levels of AD are correlated with IL-6 levels( r =0.27, p<0.05 ). (3) RANKL mRNA was significantly increased in MH7A after treated with AD and IL-6. (4) rAAV2-adiponectin was successfully produced. High level of adiponetin was detected after infected THP-1. But no significant changes in inflammatory factors (IL-1β, IL-6, and TNF-α) were found between with and without transfected THP-1.Conclusion: AD and HB-EGF may play an important role in the chronic inflammation of rheumatoid arthritis. Advanced research focused on the resource of AD and HB-EGF, and the pathogenesis AD and HB-EGF take part in may give a new hope in treatment of RA.
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