Inhibitory effects of luteolin on titanium particle-induced osteolysis in a mouse model

Wear particles liberated from the surfaces of an implanted prosthesis are associated with peri-implant osteolysis and subsequent aseptic loosening. In the latter wear particle-induced inflammation and osteoclastogenesis have been identified as critical factors, and their inhibition as important steps in the treatment of affected patients, such as those undergoing total hip replacement. In this study the ability of luteolin to inhibit both titanium (Ti) particle-induced osteoclastogenesis in vitro and osteolysis in a murine calvaria Ti particle-induced model of osteolysis was examined. The results showed that luteolin, a highly potent and efficient inhibitor of tumor necrosis factor α (TNF-α) and interleukin-6 expression, inhibited Ti particle-induced inflammatory cytokine release, osteoclastogenesis, and bone resorption in bone marrow macrophages. Microcomputed tomography and histological analyses showed that the Ti particles caused significant bone resorption and increased TRAP⁺ multinuclear osteoclasts in the murine calvarial model of osteolysis, whereas this was not the case in the luteolin treatment group, in which osteolytic suppression was accompanied by a decrease in both TNF-α production and serum levels of the osteoclast marker the C-terminal telopeptide fragment of type I collagen. These results support the use of luteolin as a natural compound in the prevention and treatment of aseptic loosening after total replacement arthroplasty.