Expressão de moduladores da via Wnt por sinoviócitos fibroblasto símile de pessoas com doenças articulares inflamatórias

Abstract

Background Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) are examples of inflammatory joint diseases (IJD) with different joint remodeling patterns. The FLS are involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involve inflammatory cytokines such as TNFa, IL17 and IL22 directly or through signaling pathways such as Wnt. Objectives To evaluate the expression of two extracellular modulators (sFRP3/Frzb and Dkk1) of the Wnt pathway by FLS of patients with different IJD, in response to IL17, IL22 or TNFa. Methods FLS were cultivated from the synovial fluid of patients with DAI. The levels of Dkk1 and sFRP3/Frzb were measured by ELISA in the culture supernatants after different doses of IL17, IL22 and TNF. The concentrations of Dkk1, sFRP3/Frzb, TNFa, IL17 and IL22 were also measured in the synovial fluid by ELISA. Results sFRP3/Frzb and Dkk1 are constitutively expressed by FLS. IL22 and sFRP3/Frzb were positively correlated (r=0.76; p<0.01) in synovial fluid and higher levels of IL22 and sFRP3/Frzb were observed among TNFa inhibitors users (p = 0.01). The stimulation with IL22 to FLS was able to increase its production of sFRP3/Frzb, but not of DKK1, with greater effects seen at doses of 1 and 10 ng/ml and time intervals between stimulus and collecting of 24 and 48 hours (p <0.01). TNFa and IL17 did not alter the basal expression of sFRP3/Frzb or Dkk1 by FLS. Conclusions - IL22 and sFRP3/Frzb are positively correlated in the IJD and IL22 induces increased expression of sFRP3/Frzb by FLS. Given the capability of sFRP3/Frzb to block the osteoblastogenesis, IL22 can be related to different patterns of structural damage and joint remodeling.