UC San Diego

The articular cartilage and underlying subchondral plate, comprised of calcified cartilage and a continuous plate of subchondral bone, form the osteochondral unit which bears and transmits the load as well as maintains low hydraulic conductivity and permeability. Age-related degeneration transitions to osteoarthritis (OA) a disease that results in degeneration of articular cartilage and abnormality of the

subchondral plate. The mechanism of this transition is not well known, and likely involves interplay between both the bone and the cartilage. This dissertation aims to delineate the biological and structural changes that occur in the osteochondral interface with age-related degeneration and disease, to help gain a better understanding of the pathogenesis.

3-D morphometric analyses of the subchondral plate in microCT indicated that the tidemark was disrupted and roughened in the early stage of degeneration. Investigating the subchondral plate in histology and with Digital Volumetric Imaging revealed that the disruptions were often caused by penetrating vascular channels that are involved in bone remodeling, which become larger and more abnormal in morphology in early degeneration stages. The penetration and disruption of the tidemark was found to occur in an earlier stage than large changes in the chondrocyte organization and fissuring of the articular cartilage matrix, known hallmarks of OA. Because the disrupted interface can potentially compromise the subchondral plate’s ability to act as a barrier to water and solutes, there is the potential of a mechanism where remodeling of the subchondral plate leads to more catabolism and fluid depressurization in the cartilage.

These studies provide new technical developments in the ability to analyze three-dimensional datasets computationally, and reduce them to morphometric parameters, allowing a multiscale assessment of the tissue depending on the region of focus and size of targeted objects. They provide quantitative confirmation of known histological hallmarks of degeneration and OA in both the cartilage and subchondral plate. Additionally, they provide novel 3-D information about the structure of the human subchondral plate in degeneration and OA, which has been mostly limited to studies of normal tissue in the past.