Piezo1 Modulates Synovial Macrophage Function to Influence the Progression of TMJ Arthritis.

Objectives: Synovial macrophages are pivotal regulators of the immune response in temporomandibular joint (TMJ) arthritis. This study investigates Piezo's regulatory effects on macrophage polarization and function in TMJ arthritis progression.

Methods: A complete Freund's adjuvant (CFA) induced TMJ arthritis model was established in C57BL/6JNifdc mice, with saline as control. The treated group received Piezo1 inhibitor GsMTx4. Synovitis severity, cartilage degradation, and bone resorption were evaluated by morphological and radiological analyses. Macrophage infiltration, Piezo1, and inflammatory cytokines were analyzed via immunohistochemistry and immunofluorescence. WB and qPCR were used to study signaling pathways in bone marrow-derived macrophages (BMDMs) treated with Piezo1 siRNA, GsMTx4, and Yoda1.

Results: Compared to the Saline group, the CFA group exhibited significant infiltration of pro-inflammatory macrophages and prominent osteochondral lesions. Furthermore, IF revealed co-localization of Piezo1, MMP13, MMP3, and TNFα with CD86 macrophages. In vitro studies demonstrated that Piezo1 activates pro-inflammatory macrophages through the NF-κB pathway, whereas it suppresses anti-inflammatory macrophage polarization by inhibiting the STAT6 pathway. GsMTx4 treatment notably alleviated arthritis symptoms.

Conclusions: The disturbed balance between pro-inflammatory and anti-inflammatory macrophages in synovitis may contribute to TMJ arthritis progression. Piezo1 modulates macrophage transcriptional regulation and polarization, influencing immune responses within the synovial environment and offering a potential therapeutic target for TMJ arthritis.