Details

Autor(en) / Beteiligte

• Gao, Ye
• Xin, He
• Cai, Bolei
• Wang, Le
• Lv, Qianxin
• Hou, Yan
• Liu, Fuwei
• Dai, Taiqiang
• Kong, Liang

Titel

RNA interference-based osteoanabolic therapy for osteoporosis by a bone-formation surface targeting delivery system

Ist Teil von

• Biochemical and biophysical research communications, 2022-04, Vol.601, p.86-92

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •We proposed a potential RNAi-based osteoanabolic treatment for osteoporosis.•The (DSS)6-Liposome delivery system could specifically target bone formation surface.•RNAi-based gene therapy enhances bone biomechanical characteristics significantly.