Single monoiodoacetic acid injection reveals toll-like receptor, oestrogen, oxidative stress, and altered energy metabolism as key drivers of temporomandibular joint osteoarthritis in female rats

Abstract

Objectives

This study aimed to establish a reproducible and minimally invasive rat model of temporomandibular joint osteoarthritis (TMJ-OA) using intra-articular monoiodoacetic acid (MIA) injection, and to investigate the pathological mechanisms underlying TMJ-OA development, aimed at providing insights for potential clinical treatments.

Design

We compared the effects of single versus multiple MIA injections on body weight, pain behaviour, and condylar pathology in female Sprague–Dawley rats. We longitudinally assessed the progression of TMJ-OA over 5 weeks by evaluating condylar pathology and immunohistochemical staining. We investigated the potential mechanism of MIA-induced TMJ-OA through transcriptome sequencing and polymerase chain reaction validation.

Results

A single MIA injection (0.5 mg) into the joint space effectively induced TMJ-OA in rats and sustained inflammatory reactions and pain without significantly affecting weight. MIA continuously promoted the development of TMJ-OA through the activation of the toll-like receptor pathway, oestrogen metabolism promotion, oxidative stress response enhancement, and energy metabolism alteration in condylar chondrocytes.

Conclusion

We have presented a simple and minimally invasive method for modelling TMJ-OA in rats, which can be utilised in animal trials focusing on TMJ-OA treatment strategies. The study also reveals toll-like receptor, oestrogen, oxidative stress, and altered energy metabolism as key drivers of TMJ-OA in female rats.