Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis
Smoking-related osteoporosis (SROP) is characterized by reduced bone mass, primarily due to the accumulation of tobacco-derived toxins. This study demonstrates the activation of ferroptosis and reactive oxygen species (ROS)-related pathways in the bone marrow mesenchymal stem cells (BMSCs) of SROP m...
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Elsevier
2025-04-01
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| Series: | Materials Today Bio |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425000596 |
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| author | Yao Wang Lin Sun Zhenglin Dong Tianyu Zhang Leining Wang Yihui Cao Hui Xu Chenglei Liu Bo Chen |
| author_facet | Yao Wang Lin Sun Zhenglin Dong Tianyu Zhang Leining Wang Yihui Cao Hui Xu Chenglei Liu Bo Chen |
| author_sort | Yao Wang |
| collection | DOAJ |
| description | Smoking-related osteoporosis (SROP) is characterized by reduced bone mass, primarily due to the accumulation of tobacco-derived toxins. This study demonstrates the activation of ferroptosis and reactive oxygen species (ROS)-related pathways in the bone marrow mesenchymal stem cells (BMSCs) of SROP mice. Here, we integrated genetic engineering and bone-targeting peptide modification to develop innovative bone-targeting engineered exosomes. Using genetic engineering techniques, we introduced α-1,3-fucosyltransferase 6 (Fut6), a key protein involved in prostate cancer bone metastasis, and identified exosomes expressing Fut6 (F6-exo) with bone-targeting capabilities. Additionally, we modified these exosomes with a bone-targeting peptide, (AspSerSer)6, to synthesize F6-(DSS)6-exo. F6-(DSS)6-exo enabled the targeted delivery of curcumin, restoring the osteogenic differentiation potential of BMSCs and mitigating bone loss in SROP mouse models. In summary, this study highlights the combination of genetic engineering and hydrophobic diacylglycerol insertion as a novel targeted therapeutic approach for SROP. |
| format | Article |
| id | doaj-art-829152e698764a80a985ad6d87ec5587 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Materials Today Bio |
| spelling | doaj-art-829152e698764a80a985ad6d87ec55872025-01-30T05:14:50ZengElsevierMaterials Today Bio2590-00642025-04-0131101501Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosisYao Wang0Lin Sun1Zhenglin Dong2Tianyu Zhang3Leining Wang4Yihui Cao5Hui Xu6Chenglei Liu7Bo Chen8Department of Hand and Foot Surgery, Beilun Branch of the First Affliated Hospital, College of Medicine. Zhejiang University, Ningbo, China; Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBengbu First People's Hospital, Bengbu, ChinaDepartment of Hand and Foot Surgery, Beilun Branch of the First Affliated Hospital, College of Medicine. Zhejiang University, Ningbo, ChinaDepartment of Hand and Foot Surgery, Beilun Branch of the First Affliated Hospital, College of Medicine. Zhejiang University, Ningbo, ChinaBengbu First People's Hospital, Bengbu, ChinaDepartment of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author.Corresponding author.; Department of Hand and Foot Surgery, Beilun Branch of the First Affliated Hospital, College of Medicine. Zhejiang University, Ningbo, China; Department of Orthopedic Surgery, The First Affliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Bengbu First People's Hospital, Bengbu, ChinaSmoking-related osteoporosis (SROP) is characterized by reduced bone mass, primarily due to the accumulation of tobacco-derived toxins. This study demonstrates the activation of ferroptosis and reactive oxygen species (ROS)-related pathways in the bone marrow mesenchymal stem cells (BMSCs) of SROP mice. Here, we integrated genetic engineering and bone-targeting peptide modification to develop innovative bone-targeting engineered exosomes. Using genetic engineering techniques, we introduced α-1,3-fucosyltransferase 6 (Fut6), a key protein involved in prostate cancer bone metastasis, and identified exosomes expressing Fut6 (F6-exo) with bone-targeting capabilities. Additionally, we modified these exosomes with a bone-targeting peptide, (AspSerSer)6, to synthesize F6-(DSS)6-exo. F6-(DSS)6-exo enabled the targeted delivery of curcumin, restoring the osteogenic differentiation potential of BMSCs and mitigating bone loss in SROP mouse models. In summary, this study highlights the combination of genetic engineering and hydrophobic diacylglycerol insertion as a novel targeted therapeutic approach for SROP.http://www.sciencedirect.com/science/article/pii/S2590006425000596 |
| spellingShingle | Yao Wang Lin Sun Zhenglin Dong Tianyu Zhang Leining Wang Yihui Cao Hui Xu Chenglei Liu Bo Chen Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis Materials Today Bio |
| title | Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis |
| title_full | Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis |
| title_fullStr | Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis |
| title_full_unstemmed | Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis |
| title_short | Targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking-related osteoporosis |
| title_sort | targeted inhibition of ferroptosis in bone marrow mesenchymal stem cells by engineered exosomes alleviates bone loss in smoking related osteoporosis |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000596 |
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