Molecular modulation of articular cartilage degradation

Cartilage homeostasis is maintained due to a balance between anabolic and catabolic processes, that are regulated by a complex network of signaling pathways. Disturbance of one or more of these pathways disrupts this balance, resulting in excessive breakdown of the extracellular matrix and ultimately cartilage degeneration. Thorough understanding of the pathways that are involved in maintaining cartilage homeostasis and that are deregulated in cartilage degradation, might provide possible therapeutic options for cartilage repair. This thesis describes the involvement of several molecular signaling pathways in articular cartilage homeostasis and cartilage degradation. After the general introduction to this thesis in chapter 1, the important role of Wnt signaling in cartilage development and disease was reviewed in chapter 2. Based on the involvement of Wnt signaling in both cartilage development and disease, chapter 3 describes the e ect of small molecule inhibitors of Wnt signaling on cytokine induced cartilage degradation in mouse fetal metatarsals. Inhibition of Wnt signaling e ectively blocked cartilage degradation by downregulation of MMP expression, without a ecting the expression of cartilage matrix components.