Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment

IF 10.8 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

International Journal of Oral Science Pub Date : 2025-02-01 DOI:10.1038/s41368-024-00329-5

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

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引用次数: 0

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.

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来源期刊

International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

31.80

自引率

1.30%

发文量

审稿时长

>12 weeks

期刊介绍： The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.