BMPR-IB on UHMWPE-induced bone destruction in the murine air pouch model

• 作 者: Yang Wang Ning-Ning Wu Min-Hu Yu-Qin Mou Rui-Dong Li Liang Chen Bai-Cheng He Zhong-Liang Deng
• 机 构: Department of Orthopaedics,Second Affiliated Hospital of Chongqing Medical University,Chongqing,4000
• 出 处: 第十届中国南方骨质疏松论坛暨重庆市医学会骨质疏松年会
• 发表日期: 2014年6期
• 关键词: BMPR-IB siRNA osteolysis air pouch model aseptic loosening

　　Objective Adenovirus expressing siRNA targeting BMPR-IB was locally administered into the air pouch of mice to improve bone resorption induced by UHMWPE particles.Method 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 ultra-high- molecular-weight polyethylene (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 (MS siRNA),virus-free culture medium (control group) into the pouches,respectively.The tissues were harvested at 14 days after 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,BMPR- IB siRNA inhibited osteoclast differentiation by targeting osteoblast for the induction of OPG formation and down-regulation of RANKL production.Conclusions This study suggested that loss of BMP signaling by BMPR-IB siRNA directs osteoblasts to decrease bone destruction in part by down-regulating osteoclastogenesis through the RANKL-OPG 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.