RNA interference-based osteoanabolic therapy for osteoporosis by a bone-formation surface targeting delivery system
RNA interference (RNAi)-based gene therapy that promotes anabolic bone formation is an effective approach for addressing osteoporosis. However, the selection of target gene and tissue-specific delivery systems has hindered the progression of this strategy. In this study, we identified casein kinase-2 interacting protein-1 encoding gene ( Ckip-1 ), a negative regulator of bone formation, as an effective target of small interfering RNAs (siRNAs) for improving bone mass. Moreover, an impressive (DSS) 6 -Liposome (Lipos) nanoparticle system that could target the bone formation surface was synthesized to enhance the delivery of Ckip-1 siRNA to osteogenic lineage cells. The in vitro results confirmed that the (DSS) 6 -Lipos system could efficaciously improve the intracellular delivery of Ckip-1 siRNA without obvious cell toxicity. The in vivo application of the delivery system showed specific accumulation of siRNA in osteogenic cells located around the bone formation surface. Bone-related analysis indicated increased bone mass and improved bone microarchitecture in mice with ovariectomy-induced osteoporosis. Moreover, the biomechanical characteristics of the tibia were enhanced significantly, indicating increased resistance to fragile fracture induced by osteoporosis. Thus, (DSS) 6 -Lipos- Ckip-1 siRNA-based osteoanabolic therapy may be a promising option for the treatment of osteoporosis.
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