TRIM31: A Novel Guardian Against Periodontal Inflammation via Modulation of NLRP3 Inflammasome and Macrophage...

Periodontitis involves dysregulated immunity where the NLRP3 inflammasome plays a key role, while the role of TRIM31, an E3 ubiquitin ligase, remains unknown in periodontitis.

Human gingival fibroblasts (HGFs) and macrophages were stimulated with LPS and ATP; TRIM31 was overexpressed via AAV, and NLRP3 was knocked out via CRISPR; periodontitis was induced in WT and NLRP3-KO mice treated with AAV-TRIM31; bone loss, osteoclasts, and apoptosis were assessed.

TRIM31 was downregulated in inflammation and correlated with M2 polarization. TRIM31 overexpression protected HGFs, promoted M2 polarization, and bound to NLRP3, thereby promoting K48-linked ubiquitination and degradation. In vivo, TRIM31 reduced bone loss, osteoclasts, and apoptosis; these effects were abolished in NLRP3-KO cells and mice.

TRIM31 negatively regulates periodontal inflammation via ubiquitin-dependent NLRP3 degradation.