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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Autores principales:	Yongzhi Cui, Yuanyuan Guo, Li Kong, Jingyu Shi, Ping Liu, Rui Li, Yongtao Geng, Weihang Gao, Zhiping Zhang, Dehao Fu
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2022
Materias:	Exosomes MSCs siRNA Bone targeting peptide Osteoporosis therapy Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2ac56068963c46cf931e989c64e9bcbc
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spelling	oai:doaj.org-article:2ac56068963c46cf931e989c64e9bcbc2021-11-28T04:35:42ZA bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis2452-199X10.1016/j.bioactmat.2021.09.015https://doaj.org/article/2ac56068963c46cf931e989c64e9bcbc2022-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21004333https://doaj.org/toc/2452-199XThe 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.Yongzhi CuiYuanyuan GuoLi KongJingyu ShiPing LiuRui LiYongtao GengWeihang GaoZhiping ZhangDehao FuKeAi Communications Co., Ltd.articleExosomesMSCssiRNABone targeting peptideOsteoporosis therapyMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 10, Iss , Pp 207-221 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Exosomes MSCs siRNA Bone targeting peptide Osteoporosis therapy Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
spellingShingle	Exosomes MSCs siRNA Bone targeting peptide Osteoporosis therapy Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	bone-targeted engineered exosome platform delivering sirna to treat osteoporosis
publisher	KeAi Communications Co., Ltd.
publishDate	2022
url	https://doaj.org/article/2ac56068963c46cf931e989c64e9bcbc
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A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

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