Evaluating Knee Osteoarthritis Induction Methods in Small Translational Animal Models from ۱۹۷۰-۲۰۲۵: A Comprehensive Systematic Review

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 ۱۹۷۰ to February ۲۰۲۵) 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 ۵,۷۰۲ records, ۹۸ studies met the inclusion criteria. Surgical (n = ۳۴), chemical (n = ۱۵), genetic (n = ۱۳), mechanical (n = ۱۹), and high-fat diet–induced (n = ۶) 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 C۵۷BL/۶ 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 ۸ 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)

کلیدواژه ها:

Animal model ، induction method ، knee ، Osteoarthritis ، Rabbit ، rodents