The Effect And Mechanism Of Anthocyanin On CoCrMo Particle-induced Osteolysis In A Mouse Calvarial Model

Purpose:Wear-particle induced osteolysis and bone resorption have been identified as the critical factors of implant failure and total joint revision.It is known that nuclear factor kappa B(NF-?B)signaling and chronic inflammation have been shown to play key roles.Although anthocyanin is known to have anti-inflammatory function via blocking NF-?B pathway,it is still unclear if anthocyanin has a protective effect on particle-induced osteolysis.In the present study,we aimed to: i)establish the mouse calvarica model of metal particle-induced(CoCrMo vs Ti)osteolysis;ii)investigate the effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model.Methods:One hundred forty healthy male BABL/c mice were divided randomly into five groups: i)sham group(sham operation and injection with PBS);ii)vehicle group I(CoCrMo particle treatment and injection with PBS);iii)vehicle group II(Ti particle treatment and injection with PBS);iv)low-dose anthocyanin group(CoCrMo particle treatment and injecting anthocyanin with 0.1 mg/g/day),and v)high–dose anthocyanin group(CoCrMo particle treatment and injecting anthocyanin with 0.4 mg/g/day).Mice were sacrificed after two weeks,harvesting the calvariae tissue for in depth analysis by micro-CT,histomorphometry,immonohistochemical and molecular biology analysis.Results:CoCrMo and Ti particles can significantly induce mice bone osteolysis,local osteoclast activation,stimulates release of inflammatory factors;in addition CoCrMo particles has better induction ability of osteolysis in mice than titanium particles.Anthocyanin markedly inhibited CoCrMo particle–induced inflammatory infiltration and decreased bone loss in vivo.Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand(RANKL)/osteoproteger(OPG)and suppressed osteoclast formation in CoCrMo particle–stimulated calvariae.Additionally,anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-?,interleukin-1? and interleukin-6 in the calvariae of CoCrMo-stimulated mice.Furthermore,we confirmed that anthocyanin attenuated osteolysis by blocking NF-?B pathway via inhibiting inhibitor of nuclear factor kappa-B kinase ?/?(IKK?/?)phosphorylation.Conclusions:Our study demonstrated that anthocyanin can protect against CoCrMo particle–induced inflammatory osteolysis via inhibiting the IKK?/?-NF-?B pathway,and have a potential therapeutic effect on the treatment of wear particle–induced osteolysis.