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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

Aging - 15(2023), 22 vom: 29. Nov., Seite 13452-13470

Sprache:

Englisch

Beteiligte Personen:

Cui, Tiehan [VerfasserIn]
Lan, Yun [VerfasserIn]
Yu, Fei [VerfasserIn]
Lin, Suai [VerfasserIn]
Qiu, Jiaxuan [VerfasserIn]

Links:

Volltext

Themen:

BBX060AN9V
Ferroptosis
Hydrogen Peroxide
Journal Article
MAPK pathways
Plumbagin
Research Support, Non-U.S. Gov't
Temporomandibular joint osteoarthritis
YAS4TBQ4OQ

Anmerkungen:

Date Completed 07.12.2023

Date Revised 14.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.18632/aging.205253

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365234141