The effect of adenovirus-mediated siRNA targeting BMPR-II on UHMWPE-induced osteoclast formation.
Aseptic loosening (AL) is the single most common complication of total joint arthroplasty. The critical factor may contribute to loosening is the adverse tissue response to wear debris. A growing body of literature suggests that BMPs influence the formation and activity of osteoclasts, and BMP signaling plays an important role in the osteoclast formation. In this study, we have employed an RNA interference approach by transfecting a small interfering RNA (siRNA) specific for BMPR-II, to determine the possible importance of this receptor as a target for UHMWPE (Ultra high molecular weight polyethylene) induced osteoclastogenesis in the air pouch model in vivo. Meanwhile, in order to further elucidation of the mechanism of BMPR-II signaling pathway in osteoclast formation, we investigated the effects of siBMPR-II toward RANKL induced osteoclast differentiation in vitro. The present study showed that locally injection of adenovirus-mediated siRNA targeting BMPR-II appears to be a feasible and effective candidate to treat or prevent wear debris-associated osteolysis. Furthermore, we revealed that the effects of BMPR-II signaling on osteoclast formation are mediated directly by osteoclast itself, as well as indirectly by altered expression of RANKL and OPG in osteoblast.
Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Yang
Y
Wang
Ning-Ning
NN
Wu
Yu-Qin
YQ
Mu
Ran-Xi
RX
Zhang
Min
M
Hu
Rui-Dong
RD
Li
Liang
L
Chen
Bai-Cheng
BC
He
Zhong-Liang
ZL
Deng
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D011095:Polyethylenes / Q000494:pharmacology*; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013194:Staining and Labeling; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; D053244:Osteoprotegerin; D011095:Polyethylenes; D034741:RNA, Small Interfering; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C111601:ultra-high molecular weight polyethylene; D052006:Bone Morphogenetic Protein Receptors, Type II; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase