Development of a sheep model of knee osteoarthritis and preliminary magnetic resonance–guided focused ultrasound evaluation

Knee osteoarthritis (KOA) is a prevalent and disabling disease with limited nonsurgical options for pain management. Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique for targeted thermal ablation and has emerged as a potential therapy for pain control. Large-animal models that better replicate human joint anatomy are needed for translational evaluation. Although monosodium iodoacetate (MIA) is widely used to induce KOA in small animals, its application in sheep remains limited. KOA was induced in the right knees of nine sheep using intra-articular MIA injections on days 8 and 29, with contralateral knees serving as controls. Animals were monitored for 12 weeks with serial behavioral and radiographic assessments. MRgFUS treatment was performed between weeks 6 and 8 after the first MIA injection. At the study endpoint, knee joints were obtained for macroscopic and histological evaluation. MIA-treated knees demonstrated radiographic features of KOA, including joint space narrowing and osteophyte formation. Gross and histological analyses confirmed cartilage degeneration, with surface erosion, reduced proteoglycan staining, and disrupted cartilage architecture. Despite consistent structural changes, only two animals developed persistent pain-related behaviors. In these animals, MRgFUS treatment was associated with improved pain scores and activity levels. No treatment-related increases in pain, functional impairment, or tissue damage were observed. Intra-articular MIA injection produced a reproducible structural model of KOA in sheep. MRgFUS was well tolerated and exhibited preliminary potential for pain relief, supporting further evaluation in larger controlled studies.