Biological responses induced by titanium particles with adherent bacterial debris or by endotoxin-free titanium particles. A, osteolysis was measured in wild type mice, TLR2−/− mice, TLR4−/− mice, or double knock-out mice lacking both TLR2 and TLR4. The results (means ± S.E. of 36–46 parietal bones/group) are presented as percentages of parietal bone contained within osteolytic regions. B, TNFα mRNA expression was measured in bone marrow macrophages isolated from wild type mice, TLR2−/− mice, TLR4−/− mice, or double knock-out mice lacking both TLR2 and TLR4. The results (means ± S.E. of five experiments) are presented as percentages of TNFα expression following incubation of wild type macrophages with titanium particles with adherent bacterial debris. Ti, titanium; wt, wild type; KO, knock-out; adh, adherent; “endo-free”, endotoxin-free; NS, not significant.