Aseptic loosening remains the primary cause of failure in total joint arthroplasty. Implant-derived particles are thought to be a main cause of osteolysis that leads to failure of total joint arthroplasty. The nervous system has been implicated in the etiology and pathogenesis of joint diseases. Substance P (SP) immunoreactive nerve fibers have been detected in the pseudomembrane and pseudocapsular tissues of aseptic loose hip prostheses, suggesting that SP might be involved in the process of aseptic loosening. Fibroblasts are abundant in periprosthetic membrane. Neuropeptides are able to modulate cytokine production by fibroblasts. In this study, we isolated fibroblasts from periprosthetic membrane at the time of revision hip arthroplasty performed because of aseptic loosening. Fibroblasts were stimulated with titanium (Ti) particles or SP. Prostaglandin (PG) E2 and interleukin-6 (IL-6) assays were performed using enzyme-linked immunosorbent assay kit. PGE2 and IL-6 secretion by fibroblasts have been significantly increased in the presence of Ti particles or SP. Moreover SP caused significant increase in PGE2 and IL-6 production by Ti particles-stimulated fibroblasts. Thus, SP and Ti particles acted synergistically to increase PGE2 and IL-6 secretion in fibroblasts from periprosthetic membrane.
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