Mechanisms of Mucoid Degeneration in the Cruciate Ligament: Role of Denatured Aggrecan Accumulation and Tissue Dysfunction.

Purpose: The frequency of detecting mucoid degeneration of the cruciate ligament (MD-CL) as an abnormal finding on magnetic resonance imaging in daily orthopedic practice is increasing. However, much about its pathogenesis remains unknown. This study investigated the pathophysiology of MD-CL by examining biochemical and physiological aspects in addition to traditional orthopedic approaches. Results: Previous studies have shown that mucoid degeneration of the anterior CL (MD-ACL) and posterior CL (MD-PCL) varies widely in incidence and clinical presentation, but both share similar pathology, marked by histological changes from the accumulation of sulfated glycosaminoglycan. This suggests a common etiology, with anatomical differences between CLs influencing clinical manifestations. Furthermore, MD-CL lesions resolved after debulking surgery, which normalized intraligamentous pressure and circulatory dynamics, suggesting a potential role of altered intraligamentous circulation in MD-CL pathogenesis. Conclusion: MD-CL is a pathological condition caused by an imbalance between the production and efflux of denatured aggrecan, possibly due to impaired matrix turnover or interstitial fluid drainage. In active-age groups, MD-CL is induced by altered intraligamentous circulation and lymphatic drainage dysfunction, combined with denatured aggrecan overproduction linked to inflammation from various proinflammatory factors. Mechanical stress may contribute to local inflammation through mechanotransduction pathways involving neuropeptides. In older adults, age-related dysfunction of nutrient vessels and increased inflammatory cytokines lead to denatured aggrecan accumulation, while age-related impaired lymphatic drainage reduces its clearance. Both age groups may exhibit abnormal deposition of denatured aggrecan within the ligament matrix, impairing CL integrity, altering viscoelasticity, and possibly resulting in osteoarthritis and meniscus damage.