Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment
Abstract The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) “difficult-to-treat”. Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome thera...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-02-01
|
| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-024-00329-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571910429343744 |
|---|---|
| author | Wenxiu Yuan Jiaqi Liu Zhenzhen Zhang Chengxinyue Ye Xueman Zhou Yating Yi Yange Wu Yijun Li Qinlanhui Zhang Xin Xiong Hengyi Xiao Jin Liu Jun Wang |
| author_facet | Wenxiu Yuan Jiaqi Liu Zhenzhen Zhang Chengxinyue Ye Xueman Zhou Yating Yi Yange Wu Yijun Li Qinlanhui Zhang Xin Xiong Hengyi Xiao Jin Liu Jun Wang |
| author_sort | Wenxiu Yuan |
| collection | DOAJ |
| description | Abstract The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) “difficult-to-treat”. Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA. |
| format | Article |
| id | doaj-art-11207b0b195d4d65b24b089129c85b5c |
| institution | Kabale University |
| issn | 2049-3169 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj-art-11207b0b195d4d65b24b089129c85b5c2025-02-02T12:11:30ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-02-0117111610.1038/s41368-024-00329-5Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatmentWenxiu Yuan0Jiaqi Liu1Zhenzhen Zhang2Chengxinyue Ye3Xueman Zhou4Yating Yi5Yange Wu6Yijun Li7Qinlanhui Zhang8Xin Xiong9Hengyi Xiao10Jin Liu11Jun Wang12State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityLaboratory of Aging Research and Department of Geriatrics, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityLaboratory of Aging Research and Department of Geriatrics, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan UniversityAbstract The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) “difficult-to-treat”. Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.https://doi.org/10.1038/s41368-024-00329-5 |
| spellingShingle | Wenxiu Yuan Jiaqi Liu Zhenzhen Zhang Chengxinyue Ye Xueman Zhou Yating Yi Yange Wu Yijun Li Qinlanhui Zhang Xin Xiong Hengyi Xiao Jin Liu Jun Wang Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment International Journal of Oral Science |
| title | Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment |
| title_full | Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment |
| title_fullStr | Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment |
| title_full_unstemmed | Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment |
| title_short | Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment |
| title_sort | strontium alix interaction enhances exosomal mirna selectively loading in synovial mscs for temporomandibular joint osteoarthritis treatment |
| url | https://doi.org/10.1038/s41368-024-00329-5 |
| work_keys_str_mv | AT wenxiuyuan strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT jiaqiliu strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT zhenzhenzhang strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT chengxinyueye strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT xuemanzhou strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT yatingyi strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT yangewu strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT yijunli strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT qinlanhuizhang strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT xinxiong strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT hengyixiao strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT jinliu strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment AT junwang strontiumalixinteractionenhancesexosomalmirnaselectivelyloadinginsynovialmscsfortemporomandibularjointosteoarthritistreatment |