Liproxstatin-1 alleviates cartilage degradation by inhibiting chondrocyte ferroptosis in temporomandibular joint

Abstract

Ferroptosis contribute to temporomandibular joint osteoarthritis (TMJOA) lesion development is still poorly understood. In this study, we used different TMJOA animal models to detect whether ferroptosis is related to onset of TMJOA which modelling by monosodium iodoacetate (MIA), IL-1{beta}, occlusion disorder (OD) and unilateral anterior crossbite (UAC). Immunohistochemical staining and Western blot analysis were used to detect ferroptosis proteins and cartilage degradation related protein expression. Our results revealed that lower level of ferroptosis-related proteins GPX4 in cartilage layer, but the level of ACSL4 and P53 increase in that of condyle. Injection of ferroptosis inhibitor liproxstatin-1 (Lip-1) effectively decrease ACSL4, P53 and TRF expression. In vitro, IL-1{beta} induced the reduction of cartilage extracellular matrix expression in mandibular condylar chondrocytes (MCCs). Lip-1 maintain the morphology and function of mitochondria, and inhibited the aggravation of lipid peroxidation and reactive oxygen species (ROS) production which induced by IL-1{beta}. These results suggested that chondrocytes ferroptosis play an important role in the development and progression of TMJOA. Inhibition of condylar chondrocyte ferroptosis could be a promising therapeutic strategy for TMJOA. SUMMARY STATEMENTFerroptosis contributed the development and progression of Temporomandibular Joint Osteoarthritis cartilage degeneration. Lip-1 can effective improvement the cartilage degradation of condyle.