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

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 H 2 O 2 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.

Loss of β-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis

“…TMD can be caused by aging, mechanical stress, psychological stress [ 2 ] or autoimmune disease like rheumatoid arthritis [ 3 , 4 ] and SAPHO syndrome [ 5 ]. As one of the most severe subtypes of TMD, temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by progressive destruction of articular cartilage and subchondral bone resorption [ 6 ]. The clinical manifestations of the disease are varied, including joint pain, restricted mouth opening, and joint cracking, which seriously affects people’s quality of life [ 7 ].…”

α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway

“…Chondrocyte death and an imbalance in extracellular matrix (ECM) metabolism are key factors in OA pathogenesis [6]. Research has demonstrated that the induction of oxidative stress contributes to chondrocyte ferroptosis [7], ECM degradation, and the exacerbation of OA through the suppression of anabolic gene expression, notably including SOX9, COL2A1, and ACAN [8,9].…”