A Surgical Method to Establish a Murine Model of Knee Osteoarthritis using a Modified Hulth Procedure

Shaokang Zhao; Minjie Wang; Chunxiao Yang; Kwensy Djoyce Ondo; Jinman Chen; Hao Xu

doi:10.3791/70379

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Method Article

A Surgical Method to Establish a Murine Model of Knee Osteoarthritis using a Modified Hulth Procedure

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DOI:

10.3791/70379

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May 15th, 2026

Shaokang Zhao^*¹^,²^,³ , Minjie Wang^*¹^,²^,³ , Chunxiao Yang¹^,²^,³ , Kwensy Djoyce Ondo¹^,²^,³ , Jinman Chen¹^,²^,³ , Hao Xu¹^,²^,³^,⁴

¹Longhua Hospital, Shanghai University of Traditional Chinese Medicine, ²Spine Institute, Shanghai University of Traditional Chinese Medicine, ³Key Laboratory of theory and therapy of muscles and bones, Ministry of Education (Shanghai University of Traditional Chinese Medicine), ⁴School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine

^* These authors contributed equally

Summary

This protocol outlines the refined surgical steps of the modified Hulth model, providing a standardized, reproducible method for inducing experimental osteoarthritis.

Abstract

Knee osteoarthritis (KOA) is a chronic degenerative joint disease characterized by articular cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovitis, which is the most common type of osteoarthritis.

This protocol presents a surgical method to establish a murine model of knee osteoarthritis using a modified Hulth procedure. Compared to injection-induced or conventional surgical models such as destabilization of the medial meniscus (DMM) and anterior cruciate ligament transection (ACLT), the modified Hulth model induces an earlier disease onset and more severe joint inflammation. By transecting the medial collateral ligament, medial meniscus, and anterior cruciate ligament, this method disrupts the mechanical alignment of the knee joint, thereby promoting OA progression. This model is particularly suitable for studying acute OA pathology and evaluating potential therapeutic interventions. To evaluate arthritis severity, we used small-animal ultrasound combined with three-dimensional (3D) reconstruction of the joint cavity to quantify its volume and assess synovial fluid accumulation. In addition, safranin-O/fast green staining of histological sections was performed for Osteoarthritis Research Society International (OARSI) scoring to evaluate cartilage destruction.

Introduction

Knee osteoarthritis (OA) is a common, chronic, degenerative joint disease characterized clinically by pain, stiffness, limited range of motion, and muscle weakness around the knee. Its prevalence is higher in women than in men. If inadequately controlled, OA can lead to progressive loss of physical capacity, sleep disturbance, chronic fatigue, and eventual disability. As global populations age, the incidence of knee OA continues to rise, posing a substantial challenge to health-care systems and economies worldwide¹^,².

Pathophysiologically, cartilage loss represents the central featu....