title: Strontium inhibits titanium particle-induced osteoclast activation and chronic inflammation via suppression of NF-κB pathway.
abstract: Wear-particle-induced chronic inflammation and osteoclastogenesis have been identified as critical factors of aseptic loosening. Although strontium is known to be involved in osteoclast differentiation, its effect on particle-induced inflammatory osteolysis remains unclear. In this study, we investigate the potential impact and underling mechanism of strontium on particle-induced osteoclast activation and chronic inflammation in vivo and in vitro. As expected, strontium significantly inhibited titanium particle-induced inflammatory infiltration and prevented bone loss in a murine calvarial osteolysis model. Interestingly, the number of mature osteoclasts decreased after treatment with strontium in vivo, suggesting osteoclast formation might be inhibited by strontium. Additionally, low receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-α, interleukin-1β, interleukin-6 and p65 immunochemistry staining were observed in strontium-treatment groups. In vitro, strontium obviously decreased osteoclast formation, osteoclastogenesis-related gene expression, osteoclastic bone resorption and pro-inflammatory cytokine expression in bone-marrow-derived macrophages in a dose-dependent manner. Furthermore, we demonstrated that strontium impaired osteoclastogenesis by blocking RANKL-induced activation of NF-κB pathway. In conclusion, our study demonstrated that strontium can significantly inhibit particle-induced osteoclast activation and inflammatory bone loss by disturbing the NF-κB pathway, and is an effective therapeutic agent for the treatment of wear particle-induced aseptic loosening.
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.|Department of Orthopedics, Jining No. 1 people's hospital, 6, jiang kang Road, Jining, 272011, China.
authors: Shijun
authors: S
authors: Zhu
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Xuanyang
authors: X
authors: Hu
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Yunxia
authors: Y
authors: Tao
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Zichuan
authors: Z
authors: Ping
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Liangliang
authors: L
authors: Wang
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Jiawei
authors: J
authors: Shi
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Xiexing
authors: X
authors: Wu
authors: Orthopedic Institute, Soochow University, 708, ren min Road, 215006, China.
authors: Wen
authors: W
authors: Zhang
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Huilin
authors: H
authors: Yang
authors: Department of Orthopedics, Jining No. 1 people's hospital, 6, jiang kang Road, Jining, 272011, China.
authors: Zhikui
authors: Z
authors: Nie
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Yaozeng
authors: Y
authors: Xu
authors: Department of Orthopedics, Zhangjiagang Hospital of Traditional Chinese Medicine, 4, kang le Road, Zhangjiagang, 215600, China.
authors: Zhirong
authors: Z
authors: Wang
authors: Department of Orthopedics,The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors: Dechun
authors: D
authors: Geng
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D010010:Osteoclasts / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013324:Strontium / Q000494:pharmacology*; D014025:Titanium / Q000633:toxicity*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D014025:Titanium; D013324:Strontium