Effective Technical Protocol for Producing a Mono-Iodoacetate-Induced Temporomandibular Joint Osteoarthritis in a Rat Model

Abstract

An animal model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) can be effectively adjusted based on the concentration of MIA to control the onset, progression, and severity of OA as required. The rat temporomandibular joint osteoarthritis (TMJOA) model using MIA is a useful tool for studying the effectiveness of disease-modifying OA drugs in TMJOA research. However, the intricate and complex anatomy of the rat TMJ often poses challenges in achieving consistent TMJOA induction during experiments. In the previous article, a reference point was established by drawing parallel lines based on the line connecting the external ear and the zygomatic arch. However, this is not suitable for the anatomical characteristics of the rat. We used the zygomatic arch as a reference, which is a technical protocol that considers it. In our protocol, we designated a point ∼1 mm away from the point where the zygomatic arch bends toward the ear as the injection site. To ensure precise injection of MIA and increase the likelihood of inducing OA, it is recommended to insert the needle at a 45° angle so that the needle tip contacts the joint projection. To confirm TMJOA induction, we identified changes in the condyle using in vivo microcomputed tomography (CT) in a rat model of MIA-induced OA and measured the degree of pain-related inflammation using head withdrawal threshold (HWT) measurements. Micro-CT scanning revealed typical OA-like lesions, including degenerative changes and subchondral bone remodeling induced by MIA in the TMJ. Pain, a major clinical feature of OA, showed an appropriate response corresponding to the structural changes shown in micro-CT scanning. In addition, the MIA concentration suitable for long-term observation of lesions was determined through ex vivo micro-CT imaging and HWT measurements. The 8 mg concentration exhibited a significant difference compared with others, confirming the sustained presence of lesions, particularly through changes in subchondral bone over an extended period. Consequently, we have successfully established a reliable rat TMJOA induction model and identified the MIA concentration suitable for long-term observation of subchondral bone research, which will greatly contribute to the study of TMJOA—an incurable disease lacking specific treatment options. The Clinical Trial Registration number is 2021-12-208.

Impact statement

Temporomandibular joint osteoarthritis (TMJOA) is an incurable disease that currently lacks specific treatment, and recently, the association with subchondral bone has been emphasized in its research. To investigate this, it is important to establish an appropriate MIA animal model for subchondral bone research. However, due to the anatomical delicacy and complexity of the rat TMJ, creating a stable model of TMJOA has been challenging. This article presents a consistent and stable method for inducing TMJOA in rats. Additionally, visual data on the effective concentration of MIA for long-term observation of subchondral bone lesions in OA are provided. This represents a valuable step in the research of TMJOA treatment and is expected to be highly beneficial.