The effect of adenovirus-mediated siRNA targeting BMPR-II on UHMWPE-induced osteoclast formation

• Published in: Biomaterials Vol. 34; no. 1; pp. 150 - 159
• Main Authors: Wang, Yang, Wu, Ning-Ning, Mu, Yu-Qin, Zhang, Ran-Xi, Hu, Min, Li, Rui-Dong, Chen, Liang, He, Bai-Cheng, Deng, Zhong-Liang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2013
• Subjects: Acid Phosphatase - genetics; Acid Phosphatase - metabolism; Adenoviridae - drug effects; Adenoviridae - metabolism; Advanced Basic Science; Air pouch model; Animals; BMPR-II; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - ultrastructure; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Morphogenetic Protein Receptors, Type II - metabolism; Cell Differentiation - drug effects; Dentistry; Female; Fluorescent Antibody Technique; Gene Expression Regulation - drug effects; Isoenzymes - genetics; Isoenzymes - metabolism; Mice; Mice, Inbred BALB C; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoclast; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; Polyethylenes - pharmacology; Receptor Activator of Nuclear Factor-kappa B - genetics; Receptor Activator of Nuclear Factor-kappa B - metabolism; RNA Interference - drug effects; RNA, Small Interfering - metabolism; Signal Transduction - drug effects; Signal Transduction - genetics; siRNA; Staining and Labeling; Tartrate-Resistant Acid Phosphatase; UHMWPE; siRNA; Osteoclast; UHMWPE; BMPR-II; Air pouch model
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.09.059

Abstract 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.