ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
This article is part of the Research TopicCraniomaxillofacial Reconstruction: from Bench to BedsideView all 5 articles
Necrostatin1 alleviates temporomandibular joint osteoarthritis and inhibits chondrocyte senescence and necroptosis possibly via p53/MAPK downregulation
Provisionally accepted
- 1Guangzhou Medical University, Guangzhou, China
- 2bechlor of Guangzhou Medical University, Guangzhiu, China
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Temporomandibular 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 TMJOA were established by utilizing Monosodium iodoacetate (MIA) to induce TMJ-OA in rats. NEC1 was administered via intra-articular injection. Treatment with NEC1 significantly alleviated the progression of TMJ-OA in rats, reduced pain, and restored cartilage integrity. In vitro, NEC1 (40 μM) exhibited cytoprotective effects on 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.
Keywords: Temporomandibular joint osteoarthritis, Necrostatin1, cellular senescence, Necrosis, p53, MAPK
Received: 30 Oct 2025; Accepted: 26 Nov 2025.
Copyright: © 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) or licensor 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.
* Correspondence: Wei Cao
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