异常力刺激对颞下颌关节骨关节炎退变软骨细胞铁死亡调控的初步研究  

The ferroptosis is induced in degenerated temporomandibular joint osteoarthritis chondrocytes by abnormal biological force

作　　者：李清华 樊沛楠 罗沁宇 于洋 杨鸿旭 LI Qinghua;FAN Peinan;LUO Qinyu;YU Yang;YANG Hongxu(The College of Life Sciences,Northwest University,Xi'an 710127,China;State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi International Joint Research Center for Oral Diseases,Department of Oral Anatomy and Physiology and TMD,School of Stomatology,The Fourth Military Medical University,Xi'an)

机构地区：[1]西北大学生命科学学院,西安710127 [2]口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院口腔解剖生理学教研室

出　　处：《实用口腔医学杂志》2025年第2期181-188,共8页Journal of Practical Stomatology

基　　金：国家自然科学基金(编号:82001071,82471001);陕西省重点研发计划一般项目(编号:2022SF-326)。

摘　　要：目的:研究旨在阐释软骨细胞铁死亡在TMJ OA进程中发挥的关键作用,证明异常生物力是铁死亡的重要诱因。方法:观察异常生物力刺激后小鼠髁突软骨形态变化及基质成分含量,通过免疫荧光染色分析细胞内GPX4蛋白的表达,通过JC-1、ROS染色分析异常生物力刺激下细胞线粒体和活性氧的含量变化。结果:单侧前牙反UAC模型造成小鼠髁突软骨退变,软骨厚度降低、细胞外基质成分减少,伴随软骨细胞铁死亡发生,软骨细胞内铁离子堆积、线粒体功能紊乱,GPX4作为铁死亡的关键调控分子其含量显著降低,使用铁死亡和GPX4的激活剂和抑制剂分别能够调控铁死亡进程;而双侧前牙咬合抬高BAE模型造成小鼠髁突软骨增生,未发现软骨细胞铁死亡现象。结论:该研究揭示了异常咬合导致的异常生物力能够诱发髁突软骨细胞铁死亡,铁死亡是导致软骨退变细胞减少的主要因素之一,GPX4对软骨细胞铁死亡实现调节。Objective:The aim of this study is to explain the key role of chondrocyte ferroptosis in TMJ OA and demonstrate that abnormal occlusion stimulation is an important causative factor of ferroptosis.Methods:We observed the morphological changes of mouse condylar cartilage in unilateral anterior crossbite(UAC,an abnormal occlusion stimulation)and bilateral anterior elevation(BAE,a proliferation occlusion stimulation)mice by HE and SO staining,and analyzed the expression of intracellular GPX4 by immunofluorescence staining,and analyzed the changes in the content of mitochondria and reactive oxygen species by JC-1 and ROS staining.Results:The UAC caused degeneration of condylar cartilage and ferroptosis of chondrocytes in mice.The accumulation of iron ions and the dysfunction of mitochondria in chondrocytes significantly upregulated.The expression of GPX4,which is a key regulator in the regulation of ferroptosis was lowered in UAC mice condyle cartilage.Moreover,in BAE model the condylar cartilage hyperplasia was observed,but not the ferroptosis of chondrocytes.Conclusion:This study revealed that the abnormal biological force caused by abnormal occlusion could induce ferroptosis of chondrocytes,and ferroptosis is one of the main factors leading to the degeneration and thinning of condylar cartilage.GPX4 could regulate the ferroptosis of chondrocytes.

关 键 词：颞下颌关节 骨关节炎 软骨细胞 铁死亡 异常生物力 

分 类 号：R782.6[医药卫生—口腔医学]