We further investigated the underlying mechanism of local bone RAS in wear-particle-induced PPOL by examining Ti-particle-induced promotion of bone resorption and suppression of bone formation using RAW264.7 macrophages and mouse BMSCs, and determined if inhibition of ACE by perindopril could suppress Ti-particle-induced osteolysis in a murine calvarial osteolysis model. This evidence concerns the gene ACE and primary osteolysis.