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

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral diseases Pub Date : 2025-08-16 DOI:10.1111/odi.70050

Lihang Shen, Ruiliu Li, Yifei Wang, Shuo Chen, Yang He

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引用次数: 0

Abstract

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.

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Piezo1调节滑膜巨噬细胞功能影响TMJ关节炎的进展。

目的：滑膜巨噬细胞是颞下颌关节（TMJ）关节炎免疫反应的关键调节因子。本研究探讨Piezo在TMJ关节炎进展过程中对巨噬细胞极化和功能的调节作用。方法：以C57BL/6JNifdc小鼠为模型，以生理盐水为对照，建立完全Freund's佐剂（CFA）诱导的TMJ关节炎模型。治疗组给予Piezo1抑制剂GsMTx4。通过形态学和放射学分析评估滑膜炎的严重程度、软骨退化和骨吸收。免疫组织化学和免疫荧光分析巨噬细胞浸润、Piezo1和炎症因子。利用WB和qPCR技术研究Piezo1 siRNA、GsMTx4和Yoda1处理后骨髓源性巨噬细胞（bmdm）的信号通路。结果：与生理盐水组相比，CFA组促炎巨噬细胞明显浸润，骨软骨病变明显。此外，IF还发现Piezo1、MMP13、MMP3和TNFα与CD86+巨噬细胞共定位。体外研究表明，Piezo1通过NF-κB途径激活促炎巨噬细胞，而通过抑制STAT6途径抑制抗炎巨噬细胞极化。GsMTx4治疗明显缓解关节炎症状。结论：滑膜炎中促炎和抗炎巨噬细胞平衡紊乱可能促进TMJ关节炎的进展。Piezo1调节巨噬细胞的转录调控和极化，影响滑膜环境中的免疫反应，并为TMJ关节炎提供潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.