Expression profile of cytokines and chemokines in osteoarthritis patients: Proinflammatory roles for CXCL8 and CXCL11 to chondrocytes

摘要

There are interactions between immune response and destruction of articular cartilage/synovial tissue in osteoarthritis (OA), which leads to chronic inflammation and systemic failure of joints. However, the role of immunological factors in the pathogenesis of OA has not been fully elucidated. In this study, expressions of 47 cytokines and chemokines were tested in the peripheral bloods and synovial fluids from 13 normal controls (NCs) and 31 OA patients. The primary chondrocytes, which were isolated from cartilages of OA patients, were stimulated by recombinant CXCL8 and CXCL11 to analyze the proliferation, cytokine secretion, and signaling pathways. The levels of IL-17A, CXCL8, CXCL9, and CXCL11 were elevated in the serum and synovial fluids of OA patients. Moreover, expressions of CXCL8 and CXCL11 were remarkably increased in the synovial fluids of late stage OA. Stimulation of CXCL8/11 resulted in the reduction of primary chondrocytes proliferation with downregulation of G2-M stage but elevation of S stage and apoptosis cells. The secretions of proinflammatory cytokines and MMPs were also increased upon stimulation. Furthermore, CXCL8/11 stimulation induced the higher expressions of phosphorylated STAT3, NF-kappa B p50 and JNK, but not p38MAPK or ERK1/2. Our findings suggested that CXCL8 and CXCL11 promoted the apoptosis and suppressed the proliferation of chondrocytes probably via influencing JAM-STAT, NF-kappa B and iNK MAPK signaling pathway and enhancing the expressions of other proinflammatory cytokines. CXCL8/11 may aggravate the disease progression of OA, and may also be served as new therapeutic targets for treatment of OA. (C) 2016 Elsevier B.V. All rights reserved.