title: [Inhibition of aseptic loosening by receptor activator of nuclear factor kappa B ligand antibody in osteolysis model of mouse].
abstract: OBJECTIVE
  Aseptic loosening of prosthesis is associated with periprosthetical osteolysis caused by osteoclast activation. Receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL)/receptor activator of NF-kappaB (RANK) signal pathway is fundamental in osteoclast activation. To determine whether RANKL antibody can inhibit inflammatory osteolysis in a osteolysis model of mouse.
  
  
  METHODS
  Sixty female BALB/c mice (aged 8-10 weeks, weighing 18-20 g) were selected. The skull bone piece was harvested from 20 mice as the donor of bone graft; the subcutaneous air pouches (2 cm x 2 cm) models were established on the back of the other 40 mice and the skull bone piece was inserted into the air pouches. The 40 mice were equally divided into groups A (negative control group), B (positive control group), C (low-dose RANKL antibody group), and D (high-dose RANKL antibody group). At 1 day after bone graft, 0.5 mL PBS was injected into the pouch of group A, 0.5 mL PBS containing titanium particle into groups B, C, and D. At 2 days before the titanium particle was injected, RANKL antibody (0.1 mL) were injected into the pouch of group C (50 microg/mL) and group D (500 microg/mL), respectively every day for 2 days, and 0.1 mL PBS into groups A and B. At 14 days after bone implantation, the pouch membranes containing implanted bone were harvested for gross observation and histological analyse.
  
  
  RESULTS
  All mice survived to the end of experiment, and incisions healed well. The gross observation showed that inflammatory responses, exudation, and vascular proliferation were obvious in group B, and were inconspicuous in groups A, C, and D. The histological analysis showed that significantly more infiltration of inflammatory cells, more obvious bone resorption, more bone collagen loss, and more positive staining area were observed in group B than in groups A, C, and D. There were significant differences in inflammatory cell number, pouch membrane thickness, bone collagen loss, and osteoclast content between group B and groups A, C, and D (P < 0.05).
  
  
  CONCLUSIONS
  RANKL antibody can directly block RANKL/RANK signal pathway, which is an efficient therapy to inhibit bone absorption associated with implant wearing particles.
authors: Department of Orthopedics, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, PR China.
authors: Song
authors: S
authors: Zhao
authors: Tao
authors: T
authors: Cheng
authors: Xiaochun
authors: X
authors: Peng
authors: Xianlong
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D016025:Bone Transplantation; D005260:Female; D007595:Joint Prosthesis; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D010014:Osteolysis / Q000517:prevention & control*; D011475:Prosthesis Failure; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000276:immunology*
chemical_list: D000906:Antibodies; D008024:Ligands; D053246:Receptor Activator of Nuclear Factor-kappa B