Tppu Inhibits Osteoclastogenesis In Temporomandibular Joint Osteoarthritis

TPPU is a soluble epoxide hydrolase (sEH) inhibitor,increasing epoxyeicosatrienoic acids (EETs), with significant anti-inflammatory and bone-protective effects. TMJOA is a common degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, and increased osteoclast activity.This study aims to investigate the potential inhibitory effect and mechanism of TPPU on subchondral osteoclasts in TMJOA A TMJOA model was established in SD rats by intra-articular injection of sodium monoiodoacetate (MIA), followed into control, MIA, and TPPU intervention groups. A co-culture model of human endothelial cells (HUVEC) and mouse mononuclear macrophages (RAW264.7) was established, in which RAW264.7 cells were induced to differentiate into osteoclasts using RANKL and treated with TPPU. Micro-CT and histological staining were used to observe morphological changes in subchondral bone. ELISA was employed to measure EET levels, while cell fluorescence, TRAP staining, and osteoclast bone slice assays were used to assess osteoclast quantity and resorptive function. TPPU inhibited osteoclast formation and activity by increasing EET levels in endothelial cells. Compared with the MIA group, the TPPU intervention group exhibited significantly alleviated subchondral bone destruction and improved trabecular structure. In the TPPU-treated co-culture cells, osteoclast numbers were markedly reduced, bone surface resorption in the slice was significantly weakened, and osteoclast activity decreased. Additionally, TPPU regulated the NF-κB signaling pathway, suppressing osteoclast differentiation and function. These findings suggest that TPPU, as a potential therapeutic agent, may delay TMJOA progression by inhibiting osteoclast activity and provide a novel strategy for TMJOA treatment.