Temporomandibular joint osteoarthritis (TMJOA) is a debilitating condition that causes severe joint pain, restricted mobility, and progressive cartilage degradation. Despite its significant impact on patients’ quality of life, the underlying pathological mechanisms of TMJOA remain incompletely elucidated, and current therapeutic interventions often provide only limited or transient relief. Exosomes, tiny vesicles released by cells, have garnered attention as potential therapeutic agents due to their role in tissue repair and inflammation modulation. However, challenges such as limited exosome yield and inconsistent therapeutic outcomes have hindered their clinical translation. To overcome these obstacles, researchers have been actively exploring innovative strategies to optimize exosome production and enhance their therapeutic effects.
In a paper (DOI: 10.1038/s41368-024-00329-5) published in the International Journal of Oral Science on February 1, 2025 researchers from Sichuan University introduced a novel approach to improve exosome efficacy for TMJOA treatment. Their study investigates how pretreating synovial mesenchymal stem cells (SMSCs) with strontium (Sr) enhances exosome production and miRNA selectively loading, leading to improved therapeutic results in animal models of TMJOA.
The research provides a detailed analysis of how Sr pretreatment boosts the yield and therapeutic potential of SMSC-derived exosomes for treating TMJOA. The team found that Sr pretreatment increases exosome production while selectively enriching miRNA profiles. Notably, Sr treatment elevates the levels of beneficial miRNAs, such as miR-143-3p, which targets Mfsd8 and inhibits chondrocyte ferroptosis—a process contributing to cartilage degradation. At the same time, harmful miRNAs linked to disease progression are significantly reduced. In TMJOA animal models, Sr-enhanced exosomes were far more effective in preventing cartilage degradation, alleviating joint pain, and reducing osteoclast activity compared to untreated exosomes. Furthermore, the study underscores the important role of the Alix protein in Sr-induced miRNA selectively loading, pointing to Alix-mediated mechanisms as critical for optimizing exosome therapy. This research not only addresses the limitations of exosome yield and therapeutic efficacy but also proposes a novel strategy for improving treatments for TMJOA and other types of osteoarthritis.
Dr. Jun Wang, the study's lead researcher, emphasized, "Our findings demonstrate the powerful role of trace elements like Sr in enhancing the therapeutic properties of exosomes. By optimizing miRNA loading through Alix, we are able to significantly increase the effectiveness of exosome-based treatments for TMJOA and potentially other degenerative joint diseases."
This research opens up exciting new possibilities for the development of targeted therapies for TMJOA and other osteoarthritis-related conditions. By improving exosome yield and selectively loading beneficial miRNAs, these advancements could lead to more effective, minimally invasive treatments. Looking ahead, future studies will aim to translate these promising findings into clinical applications, including trials in larger animal models, and investigate the broader therapeutic potential of Alix-mediated miRNA loading for other diseases.
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References
DOI
10.1038/s41368-024-00329-5
Original Source URL
https://doi.org/10.1038/s41368-024-00329-5
Funding information
This research was supported by National Natural Science Foundation of China (Nos. 82271019, 82472149, 82471024), Sichuan Science and Technology Program (No.24ZDYF0099) and Research and Develop Program, West China Hospital of Stomatology Sichuan University (RD-03-202101) to J.W.
About International Journal of Oral Science
International Journal of Oral Science (ISSN 1674-2818) was founded in 2009 and aims to publish all aspects of oral science and interdisciplinary fields, including fundamental, applied and clinical research. Covered areas include oral microbiology, oral and maxillofacial oncology, cariology, oral inflammation and infection, dental stem cells and regenerative medicine, craniofacial surgery, dental materials, oral biomechanics, oral, dental and maxillofacial genetic and developmental diseases.