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Research Paper|Volume 15, Issue 22|pp 13452—13470

Plumbagin alleviates temporomandibular joint osteoarthritis progression by inhibiting chondrocyte ferroptosis via the MAPK signaling pathways

Tiehan Cui1,3, Yun Lan2,3, Fei Yu1,3, Suai Lin1,3, Jiaxuan Qiu1
  • 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • 2Department of Stomatology, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100039, China
  • 3Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
* Equal contribution
Received: June 30, 2023Accepted: October 12, 2023Published: November 29, 2023
https://doi.org/10.18632/aging.205253

Copyright: © 2023 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aims: The acceleration of osteoarthritis (OA) development by chondrocytes undergoing ferroptosis has been observed. Plumbagin (PLB), known for its potent antioxidant and anti-inflammatory properties, has demonstrated promising potential in the treatment of OA. However, it remains unclear whether PLB can impede the progression of temporomandibular joint osteoarthritis (TMJOA) through the regulation of ferroptosis. The study aims to investigate the impact of ferroptosis on TMJOA and assess the ability of PLB to modulate the inhibitory effects of ferroptosis on TMJOA.

Materials and methods: The study utilized an in vivo rat model of unilateral anterior crossbite (UAC)-induced TMJOA and an in vitro study of chondrocytes exposed to H2O2 to create an OA microenvironment. Various experiments including cell viability assessment, quantitative RT-PCR, western blot analysis, histology, and immunofluorescence were conducted to examine the impact of ferroptosis on TMJOA and evaluate the potential of PLB to mitigate the inhibitory effects of ferroptosis on TMJOA. Additionally, RNA-seq and bioinformatics analysis were performed to investigate the underlying mechanism by which PLB regulates ferroptosis in TMJOA.

Results: Fer-1 demonstrated its potential in mitigating the advancement of TMJOA through its inhibitory effects on ferroptosis and matrix degradation in chondrocytes, thereby substantiating the role of ferroptosis in the pathogenesis of TMJOA. Furthermore, the observed protective impact of PLB on cartilage implied that PLB can modulate the inhibition of ferroptosis in TMJOA by regulating the MAPK signaling pathways.

Conclusions: PLB alleviates TMJOA progression by suppressing chondrocyte ferroptosis via MAPK pathways, indicating PLB to be a potential therapeutic strategy for TMJOA.