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A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

Bioactive Materials 2022年第4期7卷 207-221页

作者： Yongzhi Cui Yuanyuan Guo Li Kong Jingyu Shi Ping Liu Rui Li Yongtao Geng Weihang Gao Zhiping Zhang Dehao Fu Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai200080PR China Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430022PR China Department of Pharmacy Liyuan HospitalTongji Medical SchoolHuazhong University of Science and TechnologyWuhanHubei430077PR China Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhanHubei430030PR China Department of Orthopaedics Liyuan HospitalTongji Medical CollegeHuazhong University of Science&TechnologyWuhanHubei430077PR China

The complex pathogenesis of osteoporosis includes excessive bone resorption,insufficient bone formation and inadequate vascularization,a combination which is difficult to completely address with conventional *** exosomes carrying curative molecules show promise as alternative osteoporosis therapies,but depend on specifically-functionalized vesicles and appropriate engineering ***,we developed an exosome delivery system based on exosomes secreted by mesenchymal stem cells(MSCs)derived from human induced pluripotent stem cells(iPSCs).The engineered exosomes BT-Exo-siShn3,took advantage of the intrinsic anti-osteoporosis function of these special MSC-derived exosomes and collaborated with the loaded siRNA of the Shn3 gene to enhance the therapeutic *** of a bone-targeting peptide endowed the BT-Exo-siShn3 an ability to deliver siRNA to osteoblasts *** of the osteoblastic Shn3 gene enhanced osteogenic differentiation,decreased autologous RANKL expression and thereby inhibited osteoclast ***,Shn3 gene silencing increased production of SLIT3 and consequently facilitated vascularization,especially formation of type H *** study demonstrated that BT-Exo-siShn3 could serve as a promising therapy to kill three birds with one stone and implement comprehensive anti-osteoporosis effects.

关键词： Exosomes MSCs siRNA bone targeting peptide Osteoporosis therapy

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