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Updated: May 26, 2026
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A Mouse Model of Ankle-Subtalar Complex Joint Instability
Published on: October 28, 2022
Graded ankle instability induces early osteoarthritic changes in a rat model
Kenji Murata1, Sora Kawabata2, Chiharu Takasu2
1Department of Physical Therapy, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan.
Osteoarthritis and Cartilage Open
|May 25, 2026
Summary
This study used a rat model to show that ankle instability causes cartilage degeneration and molecular changes. Macrophage-related genes like CCL2 and TRPV4 were identified, linking mechanical stress to inflammation in osteoarthritis.
Area of Science:
- Biomedical Engineering
- Orthopedics
- Molecular Biology
Background:
- Ankle sprains often lead to chronic ankle instability and post-traumatic osteoarthritis.
- Understanding the early molecular changes following joint instability is crucial for developing effective treatments.
Purpose of the Study:
- To establish a rat model of graded ankle instability to study early cartilage degeneration.
- To explore the molecular alterations in cartilage associated with mechanical laxity.
Main Methods:
- Graded ankle instability was induced by transecting ankle ligaments in rats.
- Radiographic, histological, and functional analyses were performed at multiple time points.
- Exploratory RNA sequencing identified differentially expressed genes (DEGs) in ankle cartilage.
Main Results:
- Instability severity correlated with increased anterior drawer distance and talar tilt.
- Histological analysis revealed severity-dependent cartilage degeneration.
- RNA sequencing identified 245 DEGs, with enrichment in macrophage-related genes, including CCL2 and TRPV4, linking mechanical stress to inflammation.
Conclusions:
- The developed rat model effectively simulates graded ankle instability and early cartilage degeneration.
- Molecular analysis highlights the role of inflammatory pathways in the progression of osteoarthritis due to joint instability.
