Camouflage Protein-Engineered Extracellular Vesicles Alleviate TMJ-OA by Hijacking Caspase-1 to Suppress Pyroptosis.

Authors

Yufei Liu, Jie Zhou, Yukang Wang, Zhihui Hu, Guimin Yin, Mengsen Zhu, Jianke Huo, Chenyang Zhang, Yiming Wang, Shuang Fu, Jinpeng Wan, Jie Wang, Lanju Xu, Zhiling Zhang, Shufang Wang

Published in

Journal of extracellular vesicles. Volume 15. Issue 8. Pages e70342.

Abstract

Temporomandibular joint osteoarthritis (TMJ-OA) is highly prevalent with an insidious onset. Severe inflammation and significant degenerative changes are often associated with the condition, and current clinical treatments remain inadequate. In this study, we focus on pyroptosis and engineered the camouflage protein (GSDMD-C) attached to the membrane surface of small extracellular vesicles (sEVs)-sEV-p. sEV-p has two key effects: firstly, the inherent immunomodulatory and nutritional support properties of sEVs promote the recovery of cellular function under pathological conditions; secondly, camouflage protein bind to the activated caspase-1, reducing the cleavage of endogenous GSDMD. The therapeutic effects of sEV-p were evaluated through in vitro experiments and treatment of TMJ-OA models in mice and Bama pigs. We further elucidated the mechanisms by single-cell RNA sequencing analysis. Results show that sEV-p alleviates the abnormal activation of inflammatory factors induced by pyroptosis, accompanied by a reduction in the proportion of inflammatory cells and a mitigation of acute inflammatory responses.

PMID:
42571984
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.

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