Abstract
Osteoarthritis (OA), an inflammatory form of arthritis, is characterized by synovial inflammation and cartilage destruction largely influenced by two key proinflammatory cytokines—interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Notably, levels of visfatin (a proinflammatory adipokine) are elevated in patients with OA, although the relationship of visfatin to IL-6 and TNF-α expression in OA pathogenesis has been unclear. In this study, visfatin enhanced the expression of IL-6 and TNF-α in human OA synovial fibroblasts (OASFs) in a concentration-dependent manner and stimulation of OASFs with visfatin promoted phosphorylation of extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), while ERK, p38, and JNK inhibitors or siRNAs all abolished visfatin-induced increases in IL-6 and TNF-α production. Moreover, transfection with miR-199a-5p mimics reversed visfatin-induced increases in IL-6 and TNF-α production. Furthermore, we also found that visfatin-promoted IL-6 and TNF-α production is mediated via the inhibition of miR-199a-5p expression through the ERK, p38, and JNK signaling pathways. Visfatin may therefore be an appropriate target for drug intervention in OA treatment.
Highlights
Osteoarthritis (OA), a common chronic inflammatory disorder of the synovial joint, is characterized by articular cartilage degradation, cartilage remodeling/degeneration, subchondral sclerosis and osteophyte formation [1,2,3]
We found that visfatin markedly inhibits miR-199a-5p expression in
Sioci.n201t8h, r19o,u19g0h binding to the 3 -UTRs of the human IL-6 and tumor necrosis factor α (TNF-α) ge7noef s10, thereby negatively regulating visfatin-mediated IL-6 and TNF-α expression
Summary
Osteoarthritis (OA), a common chronic inflammatory disorder of the synovial joint, is characterized by articular cartilage degradation, cartilage remodeling/degeneration, subchondral sclerosis and osteophyte formation [1,2,3]. It is known that an inflammatory reaction promotes the overexpression of macrophage-derived proinflammatory cytokines interleukin 1 β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in the synovial membrane, which induces neovascularization and inflammation as well as the production of matrix-degrading enzymes such as matrix metalloproteinases (MMPs) that lead to cartilage degradation [6,7]. IL-6 involves several biological functions and plays a key role in hematopoiesis formation [8], the innate immune response, inflammation and promotes osteoclastogenesis which is recognized as being aIntc. Nificant role played by adipocytokines, including visfatin, in mediating joint damaigneth[eV1li7isvf,e1art8i,n]s.,kaeHlgetroaowlwmethuvsfecalrce,tsotarhnfedorrbBoonlleyemmopfahrvrooicswyftaeantpidnrepcirunordsIuoLrcs-e,6disbayanvpdirsocT-eiNrnaflFlaw-mαhmitpeartaoodrdiypuoadsceitpitoiosknsiunieen, wfoohusinctdehoarthritis synovial fibmriombiclsasthtes e(OffeActsSFofs)inhsualsinn[o14t]b. Visfatin.PRreosmulotstes IL-6 and TNF-α Expression in Human Osteoarthritis Synovial Fibroblasts (OASFs). TahneOsAeSrFess.ults indicate that visfatin enhances IL-6 and TNF-α expression in human OASFs
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