Method Article

Standardized Instability-induced Animal Models for Preclinical Studies of Osteoarthritis

DOI:

10.3791/69612

December 23rd, 2025

In This Article

Summary

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This protocol aims to establish suitable animal models for researching osteoarthritis.

Abstract

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As the most prevalent joint disorder worldwide, knee osteoarthritis (OA) represents a significant global health burden, prompting extensive research into its pathogenesis and treatment strategies. Despite numerous studies, standardized methodologies for model establishment remain lacking. Thus, to address this gap, we present comprehensive, reproducible protocols for developing instability-induced animal models of osteoarthritis, specifically the Destabilization of the Medial Meniscus (DMM) model in mice and the Medial Meniscus Tear (MMT) model in rats. Furthermore, we describe a straightforward and easily implementable procedure for assessing postoperative pain thresholds and spatial gait stability, aimed at promoting methodological consistency in preclinical OA research. Histological and behavioral validation confirmed the success of both models, as Osteoarthritis Research Society International (OARSI) scores were markedly elevated, stride length was significantly altered, and mechanical pain thresholds were substantially reduced in the DMM and MMT groups compared with controls, indicating pronounced joint degeneration and hypersensitivity. These validation outcomes underscore the reproducibility and translational relevance of the two models. Thus, by providing detailed video documentation, this work promotes procedural standardization and facilitates inter-laboratory consistency, thereby enhancing the reliability and comparability of OA research outcomes.

Introduction

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Osteoarthritis (OA) is a highly prevalent degenerative joint disorder and one of the leading causes of disability worldwide1,2. Despite extensive research, the development of effective disease-modifying OA drugs (DMOADs) has been relatively slow3. It is now widely acknowledged that OA is a multifactorial disease involving complex pathological changes across multiple peri-articular tissues, including articular cartilage, subchondral bone, tendons, and synovium4,5. Effective preclinical research on the diverse pathological process....

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Protocol

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All experimental procedures were conducted in accordance with the guidelines of the Animal Ethical and Welfare Committee of Zhejiang Chinese Medical University and were approved under the protocol number IACUC-20251020-11. For the DMM surgery, male C57BL/6 mice aged 10-12 weeks were used, while male Sprague-Dawley rats weighing 200-225 g were selected for the MMT procedure. All animals were housed under specific pathogen-free (SPF) conditions and allowed a one-week acclimatization period prior to experimentation. Standard husbandry conditions were maintained, with food, water, and bedding replaced at least twice weekly to ensure animal welfare and experimental consist....

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Results

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Characterization and validation of the DMM OA mouse model
After a 1 week acclimatization period, the DMM-induced osteoarthritis (OA) model in mice was established following the procedure illustrated in Figure 1. Pathological and behavioral assessments were performed two weeks post-surgery. As shown in Figure 2A, the most pronounced degenerative changes were localized to the medial femorotibial joint. The extent of cartilage degeneration was .......

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Discussion

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This protocol provides a standardized framework for the induction and evaluation of two widely used surgical OA models. These models are particularly valuable because they closely replicate the pathophysiological features of human post-traumatic OA, thereby offering strong translational relevance. The DMM model involves transection of the medial meniscotibial ligament, whereas the MMT model entails a direct tear of the medial meniscus. In our laboratory, the DMM procedure is routinely performed in mice, as the medial men.......

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Disclosures

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All authors declare that they have no conflicts of interest.

Acknowledgements

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This study was financially supported by the Research Project of Zhejiang Chinese Medical University (Grant No. 2025JKJNTZ09) and the National Natural Science Foundation of China (Grant No. 32401092). We also extend our sincere appreciation to Hangzhou Xinyao Biotechnology Co., Ltd. for providing gait analysis services, which were essential to the successful completion of this research.

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Gait analysis systemShanghai Xin Ruan Information Technology Co., LtdXR-FP202
Liposicophthalmic ointment
MiceNanjing Institute of Model Animalsc57/bl6
Pain testing systemShanghai Xin Ruan Information Technology Co., LtdXR-XZDelectronic von Frey anesthesiometer
RatNanjing Institute of Model AnimalsS/D

References

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  1. Barnett, R. Osteoarthritis. Lancet. 391 (10134), 1985(2018).
  2. Chen, S., et al. Epidemiological trends and characteristics of osteoarthritis in China during 1990-2021. J Orthop Translat. 17 (51), 218-226 (2025).
  3. Xingyan, A., Jiao, W., Ke, X., Robert Chunhua, Z., Jiacan, S....

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Tags

Osteoarthritis ModelsInstability Induced ModelsMedial Meniscus TearDestabilization Medial MeniscusPreclinical OsteoarthritisPain Threshold AssessmentGait StabilityHistological ValidationJoint Degeneration
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