Aging modifies microstructure and material properties of mineralized cartilage and subchondral bone in the murine...

The osteochondral junction is a specialized region ensuring the biomechanical and biological integration of the unmineralized articular cartilage with the subchondral bone through an intermediate layer of mineralized cartilage. This location is of clinical relevance, being a target of osteoarthritis. While aging is considered a risk factor for osteoarthritis, the interplay between microstructural and material changes during aging and predisposing to joint degeneration is not fully clear. This is especially true for mineralized cartilage, which remains understudied despite its critical role in load transfer from unmineralized articular cartilage to bone. We investigate age-related alterations of mineralized cartilage and subchondral bone in rat tibiae of adult and aged animals using a multimodal, high-resolution, correlative analysis. Our approach includes micro-computed tomography to measure microstructural features, second harmonic generation imaging to visualize collagen organization, quantitative backscattered electron imaging to map local mineral content, and nanoindentation to obtain mechanical properties. Mineralized cartilage and subchondral bone exhibited distinct age-related modifications. At the architectural level, the subchondral plate thickened and the trabecular network became coarser, those changes being different from those observed in the metaphysis. At the tissue level, mineralized cartilage was less mineralized than bone but exhibited a greater relative increase in mineral content with age, underlying differences in mineralization. A central observation is that aging led to an abrupt transition in mineral content and mechanical properties across the interface between unmineralized and mineralized cartilage, with a conceivable impact on stress localization. Overall, these changes may alter load transfer and contribute to age-related joint degeneration. STATEMENT OF SIGNIFICANCE: The osteochondral junction is a critical yet poorly understood determinant of joint integrity and a primary site of osteoarthritis. Despite its central biomechanical role, mineralized cartilage remains largely under investigated. Here, we use a high-resolution correlative approach to reveal distinct, age-related changes in microstructure and material properties of mineralized cartilage and subchondral bone. Aging markedly steepens the mineralization gradient at the interface between unmineralized and mineralized cartilage, leading to an abrupt change in mechanical properties that may promote stress concentration and limit energy dissipation. Concurrently, mineralized cartilage becomes more mineralized, stiffer, and more brittle, with some changes more pronounced than in subchondral bone. These findings identify a previously underappreciated mechanism by which aging alters load transfer across the osteochondral interface, with implications for joint degeneration and biomimetic interface design.