# Histological and Immunohistochemical Methods in Normal and Osteoarthritic Knee Cartilage of Rat and Rabbit Models: A Literature Review

**Authors:** Ana Sabucedo-Suárez, María Permuy, Fernando Muñoz, Mónica López-Peña

PMC · DOI: 10.3390/ijms262110300 · 2025-10-23

## TL;DR

This paper reviews methods used to study knee cartilage in rat and rabbit models to understand osteoarthritis better.

## Contribution

The study systematically reviews histological and immunohistochemical techniques used in rat and rabbit osteoarthritis models.

## Key findings

- Hematoxylin–Eosin and Safranin O stains clearly differentiate healthy from osteoarthritic cartilage.
- Immunohistochemistry shows decreased type II collagen and increased matrix metalloproteinases and caspase-3 in osteoarthritis.
- Histology is useful for cartilage structure evaluation, while immunohistochemistry reveals processes like apoptosis and collagen degradation.

## Abstract

The tissue covering the bones in synovial joints is called articular cartilage. Chondrocytes produce and maintain the extracellular matrix and, based on their shape and the orientation of the collagen fibers, articular cartilage is separated into four histological zones: superficial, middle, deep, and calcified zones. Osteoarthritis is a degenerative joint disorder in which mechanical, biochemical, and inflammatory factors contribute to the disruption of the balance between extracellular matrix synthesis and degradation. This article aims to review the literature published to date by identifying the techniques most used in immunohistochemistry and histology for the detection and grading of knee osteoarthritis in rabbit/rat models. A systematic review was carried out using databases to find publications that assessed osteoarthritis in rabbit/rat knee models using histological and immunohistochemical methods. Out of 766 initial articles, 56 met the criteria. Hematoxylin–Eosin and Safranin O demonstrated clear distinctions between healthy and osteoarthritis cartilage. Immunohistochemical findings showed decreased expression of type II collagen and increased expression of matrix metalloproteinases and caspase-3 in osteoarthritis cartilage. Although both have limitations, histology stains are useful for evaluating cartilage structure and osteoarthritis progression. On the other hand, immunohistochemistry techniques support established osteoarthritis processes, including apoptosis, metalloproteinases activity, and collagen degradation. Future research should explore additional pathways to improve osteoarthritis understanding.

## Linked entities

- **Proteins:** Casp3 (caspase 3)
- **Diseases:** osteoarthritis (MONDO:0005178)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}
- **Diseases:** knee osteoarthritis (MESH:D020370), inflammatory (MESH:D007249), Osteoarthritis (MESH:D010003), degenerative joint disorder (MESH:D019636)
- **Chemicals:** Safranin O (MESH:C009195), Hematoxylin-Eosin (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12609312/full.md

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Source: https://tomesphere.com/paper/PMC12609312