title: Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/β mediated NF-κB signaling in a mouse calvarial model.
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 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/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.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: xiaokui0621@126.com.
authors.forename: Yamin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: lijuehong398728@qq.com.
authors.forename: Juehong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: binbinyouli2010@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: qh197826@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: xcpeng81@163.com.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: zyc308@126.com.
authors.forename: Yaochao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 7th Floor Orthopaedic Department, No. 6 Building, No. 600 Yishan Road, Shanghai, China. Electronic address: yschen2016@hotmail.com.
authors.forename: Yunsu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002857:Chromium / Q000633:toxicity*; D003035:Cobalt / Q000633:toxicity*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D051550:I-kappa B Kinase / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008982:Molybdenum / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D010014:Osteolysis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D000872:Anthocyanins; D016328:NF-kappa B; D002857:Chromium; D003035:Cobalt; D008982:Molybdenum; D051550:I-kappa B Kinase
keywords: Anthocyanin; CoCrMo particles; Inflammation; NF-κB pathway; Osteolysis