[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-411051-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-411051-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","necrostatin-1-alleviates-temporomandibular-joint-osteoarthritis-and-inhibits-chondrocyte-senescence-and-necroptosis-possibly-via-p53mapk-downregulation","Necrostatin-1 alleviates temporomandibular joint osteoarthritis and inhibits chondrocyte senescence and necroptosis possibly via p53/MAPK downregulation","","Necrostatin-1 (NEC1), a RIPK1-targeted necroptosis inhibitor, was investigated for its therapeutic potential in temporomandibular joint osteoarthritis (TMJ-OA), focusing on chondrocyte senescence and necroptosis. Rat TMJ-OA models were induced with monosodium iodoacetate and treated by intra-articular NEC1 injection, which reduced pain and restored cartilage integrity while slowing disease progression. In vitro, NEC1 protected rat primary condylar chondrocytes from IL-1β+TNF-α-induced senescence and necrosis, suppressing SASP-related and ECM-degradation markers, likely through downregulation of p53 and MAPK signaling.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/necrostatin-1-alleviates-temporomandibular-joint-osteoarthritis-and-inhibits-chondrocyte-senescence-and-necroptosis-possibly-via-p53mapk-downregulation/411051/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/necrostatin-1-alleviates-temporomandibular-joint-osteoarthritis-and-inhibits-chondrocyte-senescence-and-necroptosis-possibly-via-p53mapk-downregulation/411051.png","ImageObject",300,407,{"name":42,"@type":43},"Bintang","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-05","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",18,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main therapeutic focus of Necrostatin-1 in TMJ-OA?","Question",{"text":63,"@type":64},"It targets RIPK1-dependent necroptosis while addressing chondrocyte senescence, necrosis, and extracellular matrix degradation associated with TMJ-OA progression.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was TMJ-OA modeled and treated in the study?",{"text":68,"@type":64},"TMJ-OA was induced in rats using monosodium iodoacetate, and NEC1 was administered via intra-articular injection.",{"name":70,"@type":61,"acceptedAnswer":71},"Which cellular pathways were reported to be inhibited by Necrostatin-1?",{"text":72,"@type":64},"NEC1 downregulated inflammation-induced p53 and MAPK signaling pathways in rat primary condylar chondrocytes.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},411051,1790678204,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":113,"preview_page_count":4},962085564381,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","TYPE Original Research PUBLISHED 18 December 2025 DOI 10.3389/fbioe.2025.1735484  \nOPEN ACCESS  \nEDITED BY  \nYi Sun,  \nUniversity Hospitals Leuven, Belgium  \nREVIEWED BY  \nJisi Zheng,  \nShanghai Jiao Tong University, China Yi Liu,  \nSouth China University of Technology, China  \n*CORRESPONDENCE  \nQingbin Zhang,  \n [2536867558@qq.com](2536867558@qq.com)[ ](2536867558@qq.com)Wei Cao,  \n [doctor.cao@gzhmu.edu.cn](doctor.cao@gzhmu.edu.cn)  \n†These authors have contributed equally to this work  \nRECEIVED 30 October 2025  \nREVISED 23 November 2025  \nACCEPTED 26 November 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nZhang Y, Cai W, Wu A, Li R, Li X, Zheng K, Lin Y, Zhang Q and Cao W (2025) Necrostatin-1 alleviates temporomandibular joint osteoarthritis and inhibits chondrocyte senescence and necroptosis possibly via p53/ MAPK downregulation.  \nFront. Bioeng. Biotechnol. 13:1735484 .  \ndoi: 10.3389/fbioe.2025.1735484  \nCOPYRIGHT  \n© 2025 Zhang, Cai, Wu, Li, Li, Zheng, Lin, Zhang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nNecrostatin-1 alleviatestemporomandibular joint osteoarthritis and inhibits chondrocyte senescence and necroptosis possibly via p53/ MAPK downregulation  \nYing Zhang 1†, Wenyi Cai 1,2†, Antong Wu 1,3†, Rui Li 1, Xin Li 1, Kaihan Zheng 1, Yufu Lin 1, Qingbin Zhang 1* and Wei Cao 1*  \n1Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China, 2Department of Stomatology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China, 3Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, Netherlands  \nTemporomandibular joint osteoarthritis (TMJ-OA) is a prevalent oral and maxillofacial disorder characterized by a complex etiology and pathogenesis. Targeting and eliminating senescent chondrocytes is emerging as a promising therapeutic strategy for TMJ-OA. Necrostatin-1 (NEC1), a receptor-interacting protein kinase 1 (RIPK1)-targeted necroptosis inhibitor, has shown potential therapeutic effects in various skeletal disorders. However, the therapeutic implications of NEC1 in TMJ-OA, particularly regarding its effect on chondrocyte senescence, remain unclear. In this study, models of TMJ-OA were established by utilizing monosodium iodoacetate (MIA) to induce TMJOA in rats. NEC1 was administered via intra-articular injection. Treatment with NEC1 significantly alleviated the progression ofTMJ-OA in rats, reduced pain, and restored cartilage integrity. In vitro, NEC1 (40 μM) exhibited cytoprotective effects on Rat primary condylar chondrocytes (rPCCs), preserving cell viability and reducing cellular senescence markers (Cdkn1a and Cdkn2a) following IL- 1β+TNF-α treatment. Additionally, NEC1 inhibited the expression of extracellular matrix (ECM) degradation markers (MMP3, MMP9, MMP13) and programmed necrosis indicators (p-MLKL) in chondrocytes. NEC1 downregulated inflammation-induced p53 and MAPK signaling pathways in rPCCs.Thus, NEC1 demonstrated a significant capacity to slow the progression of TMJ-OA by inhibiting and alleviating condylar chondrocyte senescence, necrosis, and ECM degradation, suggesting its potential role in the treatment of TMJ-OA.  \nKEYWORDS  \ntemporomandibular joint osteoarthritis, necrostatin-1, cellular senescence, necrosis, p53, MAPK  \n","cbCaivY6ENHzFEcp","https://ap.wps.com/l/cbCaivY6ENHzFEcp","pdf",3860244,12,"English","# Introduction\n## Background and clinical burden of TMJ-OA\n## Aging, inflammation, senescence, and necroptosis mechanisms\n## Rationale for NEC1 and study aims","[{\"question\":\"What is the main therapeutic focus of Necrostatin-1 in TMJ-OA?\",\"answer\":\"It targets RIPK1-dependent necroptosis while addressing chondrocyte senescence, necrosis, and extracellular matrix degradation associated with TMJ-OA progression.\"},{\"question\":\"How was TMJ-OA modeled and treated in the study?\",\"answer\":\"TMJ-OA was induced in rats using monosodium iodoacetate, and NEC1 was administered via intra-articular injection.\"},{\"question\":\"Which cellular pathways were reported to be inhibited by Necrostatin-1?\",\"answer\":\"NEC1 downregulated inflammation-induced p53 and MAPK signaling pathways in rat primary condylar chondrocytes.\"}]","Necrostatin-1 alleviates temporomandibular joint osteoarthritis and inhibits chondrocyte senescence and necroptosis possibly via p53/MAPK downregulation | PDF",1790587216]