A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis
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 therapies. Engineered exosomes carrying curative molecules show promise as alternative ost...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X21004333 |
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| author | Yongzhi Cui Yuanyuan Guo Li Kong Jingyu Shi Ping Liu Rui Li Yongtao Geng Weihang Gao Zhiping Zhang Dehao Fu |
| author_facet | Yongzhi Cui Yuanyuan Guo Li Kong Jingyu Shi Ping Liu Rui Li Yongtao Geng Weihang Gao Zhiping Zhang Dehao Fu |
| author_sort | Yongzhi Cui |
| collection | DOAJ |
| description | 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 therapies. Engineered exosomes carrying curative molecules show promise as alternative osteoporosis therapies, but depend on specifically-functionalized vesicles and appropriate engineering strategies. Here, 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 effects. Modification of a bone-targeting peptide endowed the BT-Exo-siShn3 an ability to deliver siRNA to osteoblasts specifically. Silencing of the osteoblastic Shn3 gene enhanced osteogenic differentiation, decreased autologous RANKL expression and thereby inhibited osteoclast formation. Furthermore, Shn3 gene silencing increased production of SLIT3 and consequently facilitated vascularization, especially formation of type H vessels. Our 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. |
| first_indexed | 2024-04-24T08:20:07Z |
| format | Article |
| id | doaj.art-2ac56068963c46cf931e989c64e9bcbc |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:20:07Z |
| publishDate | 2022-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-2ac56068963c46cf931e989c64e9bcbc2024-04-17T01:31:01ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-04-0110207221A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosisYongzhi Cui0Yuanyuan Guo1Li Kong2Jingyu Shi3Ping Liu4Rui Li5Yongtao Geng6Weihang Gao7Zhiping Zhang8Dehao Fu9Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR ChinaDepartment of Pharmacy, Liyuan Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, 430077, PR ChinaTongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Pharmacy, Liyuan Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, 430077, PR ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 430077, PR ChinaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR ChinaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 430077, PR ChinaTongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR ChinaDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China; *Corresponding author. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR ChinaThe complex pathogenesis of osteoporosis includes excessive bone resorption, insufficient bone formation and inadequate vascularization, a combination which is difficult to completely address with conventional therapies. Engineered exosomes carrying curative molecules show promise as alternative osteoporosis therapies, but depend on specifically-functionalized vesicles and appropriate engineering strategies. Here, 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 effects. Modification of a bone-targeting peptide endowed the BT-Exo-siShn3 an ability to deliver siRNA to osteoblasts specifically. Silencing of the osteoblastic Shn3 gene enhanced osteogenic differentiation, decreased autologous RANKL expression and thereby inhibited osteoclast formation. Furthermore, Shn3 gene silencing increased production of SLIT3 and consequently facilitated vascularization, especially formation of type H vessels. Our 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.http://www.sciencedirect.com/science/article/pii/S2452199X21004333ExosomesMSCssiRNABone targeting peptideOsteoporosis therapy |
| spellingShingle | Yongzhi Cui Yuanyuan Guo Li Kong Jingyu Shi Ping Liu Rui Li Yongtao Geng Weihang Gao Zhiping Zhang Dehao Fu A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis Bioactive Materials Exosomes MSCs siRNA Bone targeting peptide Osteoporosis therapy |
| title | A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis |
| title_full | A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis |
| title_fullStr | A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis |
| title_full_unstemmed | A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis |
| title_short | A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis |
| title_sort | bone targeted engineered exosome platform delivering sirna to treat osteoporosis |
| topic | Exosomes MSCs siRNA Bone targeting peptide Osteoporosis therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X21004333 |
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