# Time‐ and dose‐related pathological changes in knee osteoarthritis rat model induced by monosodium iodoacetate

**Authors:** Wei Pu, Qi Liu, Shuyan Xue, Siyuan Li, Nan Nan, Yang Liu, Huiqin Hao

PMC · DOI: 10.1002/ame2.70037 · 2025-06-12

## TL;DR

This study examines how different doses and timeframes of monosodium iodoacetate injections affect knee osteoarthritis in rats.

## Contribution

The study establishes a standardized MIA-induced KOA rat model with optimal dose and time parameters for reliable long-term observation.

## Key findings

- MIA injection caused dose-dependent increases in subchondral bone density and structural changes.
- 40 mg/mL MIA was found to be the optimal dose for inducing stable pathological changes without excessive animal discomfort.
- Pathological severity increased significantly with both higher MIA doses and longer observation periods.

## Abstract

Knee osteoarthritis (KOA) is a chronic degenerative disease. Monosodium iodoacetate (MIA) induction is the most commonly used therapeutic effect evaluation and mechanism of action research model; we observed a lack of standardization and uniformity in current model building methods, which led us to conduct this study.

The aim was to investigate the time‐ and dose‐related changes in the behavioral and pathological characteristics in the MIA‐induced KOA model rat.

MIA (40, 50, and 60 mg/mL) was injected into the left joint of male Sprague–Dawley rats. After 2 weeks, the changes in the KOA rat model were observed by behavioral evaluation, imaging‐level evaluation, and histological‐level evaluation. The changes were also compared after 40‐mg/mL MIA injection for 2 and 6 weeks.

MIA‐induced bone surface defects, osteophyte hyperplasia around the articular rim, increased subchondral bone density, thinning of the sparse trabecular bone, structural disorder, and local clustering were observed. The degree of injury gradually increased with the increase in MIA concentration. After 6 weeks, subchondral bone density and sparse trabecular bone increased in the KOA model.

The severity of the model also increased significantly with the changes in dose and time. In dose‐dependent experiments, this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals. This dose may induce pathological changes stably and is suitable for long‐term observation.

Time‐ and dose‐related pathological changes of knee osteoarthritis rat model induced by monosodium iodoacetate.

## Linked entities

- **Chemicals:** monosodium iodoacetate (PubChem CID 5239)

## Full-text entities

- **Diseases:** degenerative disease (MESH:D019636), osteophyte hyperplasia (MESH:D054850), KOA (MESH:D020370), disorder (MESH:D009358), bone (MESH:D001847)
- **Chemicals:** MIA (MESH:D019807)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12907984/full.md

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Source: https://tomesphere.com/paper/PMC12907984