Ritchie Timmermans | 07-11-2023 | Application of 3D human in vitro osteoarthritic chondrocyte models to study CCN4/WISP1 and Wnt signaling
This thesis explores the role of CCN4/WISP1 and Wnt signaling in osteoarthritis (OA) using advanced 3D human in vitro chondrocyte models. OA is characterized by cartilage degeneration and altered chondrocyte behavior, which is not adequately replicated in traditional 2D cultures. Therefore, physiologically relevant 3D systems were developed to better mimic the cartilage microenvironment. The study identifies CCN4/WISP1 as a key mediator in OA, showing that its upregulation contributes to impaired cartilage homeostasis by reducing extracellular matrix production and promoting catabolic activity. In parallel, dysregulated Wnt signaling is shown to drive chondrocyte dedifferentiation and a shift toward a fibroblast-like phenotype. Using 3D models, the interaction between CCN4/WISP1 and Wnt signaling was further characterized, revealing their combined role in cartilage degradation. Overall, the findings highlight the value of 3D chondrocyte models and suggest that targeting CCN4/WISP1 and Wnt pathways may offer new therapeutic strategies for OA.