Ulinastatin(UTI), is widely used to clinically treat LPS-related inflammatory disorders recently. <br />Adherent pathogen-associated molecular patterns (PAMPs)，of which LPS is the best-studied<br /> and classical endotoxin produced by Gram-titanium particles in cell culture and animal models of implant loosening.This study was designed to explore the inhibitory effect of UTI on osteoclas-togenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw 264.7 cells and murine osteolysis models ,and investigate the potential mechanism.The vitro study was divided into the control group,LPS-induced group,PMMA-stimulated group,and UTI-pretreated group.UTI(500U/mL or 5000U/mL) pretreatment was followed by PMMA(0.5mg/mL) with adherent LPS.The levels of inflammatory mediators including TNF-α,MMP-9 and IL-6,RANK,and Cathepsin K were examined and the amounts of phosphorylated I-κB,MEK,JNK and p38 were measured. In vivo study,murine osteolysis models were divided into the control group , PMMA-induced group,and UTI-treated group.UTI(500U/kg.d or 5000U/kg.d) was injected intraperitoneally followed by PMMA suspension with adherent LPS(2×108 particles/25μl) in the UTI-treated group . The thickness of interfacial membrane and the number of infiltrated inflam-matory cells around the implants were assessed,and BMD, Tb.N, Tb.Th, Tb.Sp, relative BV/TV of distal femur around the implants were calculated.Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9,IL-6,TNF-α,RANK,and Cathepsin K through downregulating the activity of NF-κB and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.
- aseptic loosening(AL)
- ©2016 The Author(s)
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