Evaluating Knee Osteoarthritis Induction Methods in Small Translational Animal Models from 1970-2025: A Comprehensive Systematic Review

Document Type : SYSTEMATIC REVIEW

Authors

1 Center for Orthopedic Trans-Disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran -School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran , Iran

3 Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran

4 Department of Orthopedic Surgery, University of California, San Francisco, 1500 Owens Street, San Francisco, CA, USA

5 Center for Orthopedic Trans-Disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran- Department of Orthopedics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

10.22038/abjs.2025.89905.4077

Abstract

Objectives: This approaches, for inducing knee osteoarthritis (KOA) in rabbit and rodent models. It also summarizes data study evaluates surgical, mechanical, chemical, genetic, and diet-induced methods, as well as combination-based on post-intervention time points for KOA development, the duration required for osteophyte formation, KOA scoring systems, and relevant histopathological findings.
Methods: A systematic search of PubMed, Scopus, and Web of Science (from 1970 to February 2025) was conducted using the PICO framework, focusing on animal models (rabbits and rodents), osteoarthritis induction methods, comparative efficacy, and relevant outcomes. Extracted variables included model characteristics, interventions, and KOA-related findings. The risk of bias was assessed using the Cochrane risk-of-bias tool and the ROBINS-I tool.
Results: After screening 5,702 records, 98 studies met the inclusion criteria. Surgical (n = 34), chemical (n = 15), genetic (n = 13), mechanical (n = 19), and high-fat diet–induced (n = 6) models, as well as combination approaches, were reviewed. Among surgical techniques, anterior cruciate ligament transection (ACLT) and medial meniscus destabilization (DMM) were the most frequently used, whereas monosodium iodoacetate (MIA) was the predominant chemical inducer. Genetic models primarily involved gene deletions or mutations in C57BL/6 mice. Mechanical induction methods included joint loading, treadmill running, and immobilization. Histological evaluation—most commonly using the Mankin and Osteoarthritis Research Society International (OARSI) scoring systems—was the predominant approach for KOA assessment, while micro–computed tomography (micro-CT) was employed in selected studies. Osteophyte formation was prominent in surgical and specific chemical models and was typically observed within 8 weeks post-intervention. Additionally, each induction method exhibited a distinct time course for osteophyte development and the establishment of KOA.
Conclusion: Each approach offers distinct advantages for replicating KOA pathology and for facilitating research into disease mechanisms and therapeutic interventions.
Level of evidence: N/A (since this study reviews the laboratory/basic science studies)

Keywords

Main Subjects

References

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The Archives of Bone and Joint Surgery
Volume 14, Issue 4
April 2026
Pages 232-266

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History

  • Receive Date: 15 August 2025
  • Revise Date: 24 November 2025
  • Accept Date: 26 November 2025

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