Calcineurin Inhibition at Physiological Osmolarity: Toward improving cartilage regeneration

Articular hyaline cartilage is a white, smooth structure covering the ends of bones in synovial joints, like in the hip and knee. Because of its unique stiff yet flexible properties, it distributes the loads, as a consequence of weight bearing and locomotion, over the surface of the joint and enables bones to smoothly glide over each other during movement. Thus, hyaline cartilage enables us to walk, dance and run a marathon with low friction between our articulating bones, providing us quality of life. However, when damaged it mostly fails to repair itself properly.

The research that is reported in this dissertation aimed at finding new potential tools for improving cartilage matrix synthesis by chondrocytes and progenitor cells, either in vitro for cell transplantation techniques to repair focal cartilage defects or in vivo toward a treatment for osteoarthritis. The studies focus on influencing the calcineurin-dependent NFAT1-4 pathway and the osmolarity-dependent NFAT5 pathway. Especially the combination of influencing both pathways holds potential to alter the course of cartilage regeneration and osteoarthritis in the future