Age-related degeneration initiates at the surface: preferential biomechanical and biological decline in rat articular cartilage

Age-related degeneration of articular cartilage is a key pathological hallmark of primary osteoarthritis (OA). As the cartilage’s barrier layer, the superficial zone maintains tissue homeostasis and is increasingly recognized as the initial site of age-related cartilage degeneration. Disruption of this zone exposes deeper layers to hostile microenvironments, accelerating pan-cartilaginous changes; however, its age-related progression remains incompletely defined. We systematically characterized aging-associated alterations in the rat tibial plateau superficial zone across imaging, biomechanical, and biological parameters. Using integrated radiology, nanomechanical testing, and histomorphometry, we found that radiographic parameters did not differ significantly between 6 and 12 months. In contrast, the cartilage indentation modulus declined with age, and interregional disparities narrowed as degeneration progressed. Histology showed reduced cell density, hypertrophic chondrocytes, decreased proteoglycan content, and collagen structural disorganization in the superficial zone. Molecular profiling demonstrated downregulation of COL-II and PRG4, alongside upregulation of Caspase3, MMP13, and COL-X. These findings indicate that the anteromedial tibial plateau exhibits the earliest and most pronounced age-dependent degeneration within the superficial zone, characterized by architectural, biological, and mechanical alterations that precede significant subchondral bone remodeling. This work delineates the spatiotemporal progression of superficial zone aging, providing insights for early OA diagnosis and intervention.