Targeted soluble epoxide hydrolase inhibits M1 macrophage polarization to improve cartilage injury in temporomandibular joint osteoarthritis

作者：Bing Yan, Yi Li, Yiding Liu, Yu Zhang, Sha Liu, Fu Wang, Lu Gao · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07003-2 · 被引用次数：7 · 研究领域：Eicosanoids and Hypertension Pharmacology、Heme Oxygenase-1 and Carbon Monoxide、Chronic Obstructive Pulmonary Disease (COPD) Research

BACKGROUND: Macrophage immunomodulation has emerged as a novel intervention and therapeutic strategy for temporomandibular joint osteoarthritis (TMJOA), potentially serving as a key approach for reducing synovial inflammation and promoting cartilage repair. The soluble epoxide hydrolase inhibitor (sEHi), TPPU, has shown potential therapeutic effects against inflammatory diseases and osteogenesis by elevating endogenous Epoxyeicosatrienoic acids (EETs). However, it remains largely unknown whether TPPU can reduce inflammation and cartilage degradation in the TMJOA. METHODS: In vivo, the effects of TPPU on articular cartilage and synovial tissue pathology were assessed using H&E, Masson, Safranin-O/Fast Green staining and immunohistochemistry in a mouse model of TMJOA induced by unilateral anterior crossbite (UAC). RNA-seq and Western Blot was employed to investigate the key signal pathway of TPPU on M1 macrophage polarization. Subsequently, a co-culture system of macrophages and ATDC5 chondrocytes was established, and the influence of TPPU-treated macrophages on chondrogenesis was evaluated through Alcian Blue staining and RT-qPCR. RESULTS: In vivo, we observed that in UAC-induced TMJOA mice, TPPU significantly reduced the infiltration of inflammatory cells in the synovium and the positive expression of inflammatory factors TNF-α and IL-1β. It also mitigated the degradation of cartilage matrix and increased the positive expression of chondrogenic markers SOX9 and COL II. In vit...