Abstract

ABSTRACT Aims Inflammatory responses to wear debris cause osteolysis that leads to aseptic loosening and hip arthroplasty failure. Wear debris stimulate macrophages and fibroblasts to secret proinflammatory cytokines, including TNF-α and IL-6, which have been specifically implicated in periprosthetic osteolysis and osteoclast differentiation. Naringin has anti-inflammatory effect in macrophages. Moreover, naringin inhibited osteoclastogenesis and wear particles-induced osteolysis. In this study, we examined the potential inhibitory effects of naringin on titanium (Ti) particle-induced proinflammatory cytokines secretion in fibroblasts and the possible underlying molecular mechanisms. Materials and methods Fibroblasts were isolated from periprosthetic membrane at the time of revision surgery performed due to aseptic loosening after hip arthroplasty and were cultured in the presence or absence of Ti particles, naringin and mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (a selective inhibitor of ERK), SP600125 (a selective inhibitor of JNK), and SB203580 (a selective inhibitor of p38). TNF-α and IL-6 assays were performed using enzyme-linked immunosorbent assay kits. The phosphorylation levels of p38 and nuclear factor kappa B p65 (NF-κB p65) were examined by western blot. Results Naringin or SB203580 pretreatment significantly suppressed the secretion of TNF-α and IL-6 induced by titanium particles in fibroblasts, while inhibition of ERK or JNK pathways showed no effect on production of TNF-α and IL-6. Moreover, naringin inhibited Ti particle-induced phosphorylation of p38 and p65. Conclusions These results indicated that naringin could inhibit Ti particle-induced inflammation in fibroblasts by inhibiting p38 MAPK/NF-κB p65 activity and might be a potential drug for the treatment of inflammatory periprosthetic osteolysis after arthroplasty.

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