Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury
It is observed in clinical practice that worse healing in rotator cuff tear (RCT) is closely associated with osteoporosis in patients. Herein, from the statistical analysis, we further confirmed that the RCT is significantly increased in postmenopausal women who suffer from decreased bone mineral de...
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KeAi Communications Co., Ltd.
2025-09-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25002385 |
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| author | Ming Li Xinhao Li Zepeng He Yongjian Luo Zeyu Yao Jingyi Hou Yan Yan Yi Long Yongming Chen Rui Yang |
| author_facet | Ming Li Xinhao Li Zepeng He Yongjian Luo Zeyu Yao Jingyi Hou Yan Yan Yi Long Yongming Chen Rui Yang |
| author_sort | Ming Li |
| collection | DOAJ |
| description | It is observed in clinical practice that worse healing in rotator cuff tear (RCT) is closely associated with osteoporosis in patients. Herein, from the statistical analysis, we further confirmed that the RCT is significantly increased in postmenopausal women who suffer from decreased bone mineral density (BMD), suggesting intervention of osteoporosis as a potential strategy in the management of RCT in aged women. Our previous studies showed that Growth arrest-specific 5 (GAS5), a long non-coding RNA (lncRNA), could promote bone formation, and alleviate osteoporosis. Herein, we demonstrated an enhancement of RCT healing by intraarticular administration of the GAS5 delivered with lipid nanoparticles (LNPs). Firstly, different kinds of ionizable lipids were applied to screen the capability of LNPs to deliver GAS5 in vitro to bone marrow mesenchymal stem cells (BMSCs) and the best-performing lipid was applied for in vivo evaluation in treating RCT rat models with osteoporosis by intraarticular injection. We found that GAS5-LNPs could improve bone quality and macrophage transformation into M2 type of the models with osteoporosis and facilitate healing of RCT. The therapeutic outcome with RCT rats demonstrated that tendon morphology, mechanical properties and bone quality of the rotator cuff were greatly improved. Thus, this study provides a new strategy to treat RCT by improving bone quality with formulated GAS5 by LNP, which is promising for clinical application. |
| format | Article |
| id | doaj-art-5631633acd4c408dbf593b22566ea976 |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Bioactive Materials |
| spelling | doaj-art-5631633acd4c408dbf593b22566ea9762025-08-20T03:18:15ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-09-015175877310.1016/j.bioactmat.2025.06.009Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injuryMing Li0Xinhao Li1Zepeng He2Yongjian Luo3Zeyu Yao4Jingyi Hou5Yan Yan6Yi Long7Yongming Chen8Rui Yang9Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, ChinaSchool of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, ChinaThe First Affiliated Hospital of Shaoyang University, Shaoyang, 422000, Hunan, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, ChinaSchool of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, China; College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004, China; State Key Laboratory of Antiviral Drugs, Henan University, Zhengzhou, 450046, China; Corresponding author. School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, China.Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, 510120, China; Corresponding author.It is observed in clinical practice that worse healing in rotator cuff tear (RCT) is closely associated with osteoporosis in patients. Herein, from the statistical analysis, we further confirmed that the RCT is significantly increased in postmenopausal women who suffer from decreased bone mineral density (BMD), suggesting intervention of osteoporosis as a potential strategy in the management of RCT in aged women. Our previous studies showed that Growth arrest-specific 5 (GAS5), a long non-coding RNA (lncRNA), could promote bone formation, and alleviate osteoporosis. Herein, we demonstrated an enhancement of RCT healing by intraarticular administration of the GAS5 delivered with lipid nanoparticles (LNPs). Firstly, different kinds of ionizable lipids were applied to screen the capability of LNPs to deliver GAS5 in vitro to bone marrow mesenchymal stem cells (BMSCs) and the best-performing lipid was applied for in vivo evaluation in treating RCT rat models with osteoporosis by intraarticular injection. We found that GAS5-LNPs could improve bone quality and macrophage transformation into M2 type of the models with osteoporosis and facilitate healing of RCT. The therapeutic outcome with RCT rats demonstrated that tendon morphology, mechanical properties and bone quality of the rotator cuff were greatly improved. Thus, this study provides a new strategy to treat RCT by improving bone quality with formulated GAS5 by LNP, which is promising for clinical application.http://www.sciencedirect.com/science/article/pii/S2452199X25002385Lipid nanoparticlesGrowth arrest specific 5(GAS5)Rotator cuff tear (RCT)OsteoporosisMacrophage transformation |
| spellingShingle | Ming Li Xinhao Li Zepeng He Yongjian Luo Zeyu Yao Jingyi Hou Yan Yan Yi Long Yongming Chen Rui Yang Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury Bioactive Materials Lipid nanoparticles Growth arrest specific 5(GAS5) Rotator cuff tear (RCT) Osteoporosis Macrophage transformation |
| title | Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury |
| title_full | Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury |
| title_fullStr | Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury |
| title_full_unstemmed | Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury |
| title_short | Delivery of GAS5 by LNP promotes tendon-bone healing in rotator cuff injury |
| title_sort | delivery of gas5 by lnp promotes tendon bone healing in rotator cuff injury |
| topic | Lipid nanoparticles Growth arrest specific 5(GAS5) Rotator cuff tear (RCT) Osteoporosis Macrophage transformation |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25002385 |
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