title: Inhibitory effect of adenovirus-mediated siRNA-targeting BMPR-IB on UHMWPE-induced bone destruction in the murine air pouch model.
abstract: OBJECTIVE
  Adenovirus expressing small interfering RNA (siRNA)-targeting BMPR-IB was locally administered into the air pouch of mice to improve bone resorption induced by ultra-high molecular weight polyethylene (UHMWPE) particles.
  
  
  METHODS
  Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of calvaria from a syngeneic mouse donor. The bone-implanted pouches were stimulated with the UHMWPE suspension. UHMWPE-containing mice were divided into three study groups to receive injections of adenovirus expressing BMPR-IB siRNA (BMPR-IB group), adenovirus expressing missense siRNA, and virus-free culture medium (control group) into the pouches, respectively. The tissues were harvested at 14 days after the treatment for molecular and histological analyses.
  
  
  RESULTS
  Adenovirus-mediated BMPR-IB siRNA treatment significantly improved UHMWPE particle-induced bone resorption, reduced TRAP and RANK gene and protein expression levels, and diminished the number of TRAP-positive cells. Furthermore, the BMPR-IB siRNA inhibited osteoclast differentiation by targeting osteoblast for the induction of osteoprotegerin formation and downregulation of receptor for activation of nuclear factor-κB ligand production.
  
  
  CONCLUSIONS
  This study suggested that loss of bone morphogenetic protein signaling by BMPR-IB siRNA directs osteoblasts to decrease bone destruction in part by downregulating osteoclastogenesis through the receptor for activation of nuclear factor-κB ligand-osteoprotegerin pathway. Local administration of adenovirus expressing siRNA-targeting BMPR-IB may be a feasible and effective therapeutic candidate to treat or prevent wear debris-associated osteolysis.
authors: Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Yang
authors: Y
authors: Wang
authors: Ning-Ning
authors: NN
authors: Wu
authors: Min
authors: M
authors: Hu
authors: Yu-Qin
authors: YQ
authors: Mou
authors: Rui-Dong
authors: RD
authors: Li
authors: Liang
authors: L
authors: Chen
authors: Bai-Cheng
authors: BC
authors: He
authors: Zhong-Liang
authors: ZL
authors: Deng
mesh_terms: D000256:Adenoviridae; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000096:biosynthesis* / Q000235:genetics; D001862:Bone Resorption / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016025:Bone Transplantation; D004195:Disease Models, Animal; D020868:Gene Silencing; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D020959:Polyethylene / Q000009:adverse effects* / Q000494:pharmacology; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014185:Transplantation, Isogeneic
chemical_list: D053244:Osteoprotegerin; D034741:RNA, Small Interfering; C506031:Tnfrsf11b protein, mouse; D020959:Polyethylene; C498215:Bmpr1b protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I