title: Icariin protects against titanium particle-induced osteolysis and inflammatory response in a mouse calvarial model.
abstract: Periprosthetic osteolysis and subsequent aseptic loosening are common in implant failure, a complication with revision surgery being the only established treatment. Wear particle-induced inflammation and extensive osteoclastogenesis play critical roles in periprosthetic osteolysis. A recent approach in limiting osteolysis is therefore focused on inhibiting osteoclastic bone resorption. This study aimed to investigate the potential impact of icariin, the major ingredient of Epimedium, on titanium particle-induced osteolysis in a mouse calvarial model. Eighty-four male C57BL/J6 mice were divided randomly into four groups. Mice in the sham group underwent sham surgery only, whereas animals in the vehicle, low- and high-concentration icariin groups received titanium particles. Mice in the low- and high-concentration icariin groups were gavage-fed with icariin at 0.1 or 0.3 mg/g/day, respectively, until sacrifice. Mice in the sham and vehicle groups received phosphate-buffered saline daily. After 2 weeks, mouse calvariae were collected for micro-computed tomography, histomorphometry and molecular analysis. Icariin significantly reduced particle-induced bone resorption compared with the vehicle group. Icariin also prevented an increase in receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio and subsequently suppressed osteoclast formation in titanium particle-charged calvariae. In addition, immunohistochemical analysis and enzyme-linked immunosorbent assay showed icariin significantly reduced expression and secretion of tumor necrosis factor-α, interleukin-1β and interleukin-6 in the calvariae of titanium-stimulated mice. Collectively, these results suggest that icariin represents a potential treatment for titanium particle-induced osteolysis and could be developed as a new therapeutic candidate for the prevention and treatment of aseptic loosening.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China.
authors.forename: Hongguo
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Soochow University, PR China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China.
authors.forename: Jingfu
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Orthopedic Institute, Soochow University, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China. Electronic address: xuyaozeng@163.com.
authors.forename: Yaozeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China. Electronic address: szgengdc@163.com.
authors.forename: Dechun
authors.initials: D
authors.lastname: Geng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000627:therapeutic use*; D034181:Epimedium / Q000737:chemistry; D005419:Flavonoids / Q000302:isolation & purification / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010014:Osteolysis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012886:Skull / Q000187:drug effects* / Q000473:pathology; D014025:Titanium / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; C056599:icariin
keywords: Aseptic loosening; Icariin; Inflammation; Osteoclastogenesis; Wear particles