Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/β mediated NF-κB signaling in a mouse calvarial model. (May 2017)

• Record Type: Journal Article
• Authors: Li, Yamin; Li, Juehong; Li, Bin; Qin, Hui; Peng, Xiaochun; Zhao, Yaochao; Chen, Yunsu
• Is Part Of: Molecular immunology. Volume 85(2017:May)
• Page Start: 27
• Page End: 34
• Publication Date: 2017-05
• Subjects: Osteolysis -- Inflammation -- CoCrMo particles -- Anthocyanin -- NF-κB pathway; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.02.003
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: CoCrMo particles contribute to peri -prosthetic osteolysis and aseptic loosening. IKKα/β-NF-κB pathway plays a key role in wear particle-induced osteolysis. Anthocyanin suppresses particle-induced inflammation and osteoclastogenesis in-vivo . Anthocyanin blocks NF-κB signaling by inhibiting IKKα and IKKβ activation. Anthocyanin could be a potential therapy for CoCrMo particle-induced osteolysis. Abstract: Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1 mg/g/day), and 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, immunohistochemical and molecular biology analysis. As expected, 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 calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle–induced inflammatory osteolysis via inhibiting the IKKα/β-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle–induced osteolysis.