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

作者：Wenxiu Yuan, Jiaqi Liu, Jiaqi Liu, Zhenzhen Zhang, Chengxinyue Ye, Xueman Zhou, Yange Wu, Yange Wu, Yijun Li, Qinlanhui Zhang, Xin Xiong, Hengyi Xiao, Jin Liu, Jin Liu, Jun Wang · 发表于：International Journal of Oral Science · 年份：2025 · DOI：10.1038/s41368-024-00329-5 · 被引用次数：22 · 研究领域：Extracellular vesicles in disease、Musculoskeletal synovial abnormalities and treatments、Osteoarthritis Treatment and Mechanisms

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.