HypOA

Osteoarthritis is a painful and disabling disease of the locomotor system characterized by degeneration of cartilage and underlying bone. There currently is no cure. It has been identified as a serious disease determining morbidity and mortality in elderly. The number of Dutch osteoarthritis patients will almost double to 2.3 million patients in 2040. Without effective intervention in this disease the central mission of LSH to add at least five years in good health to the lives of all Dutch citizens by 2040, is unachievable. To develop an effective pharmacological treatment, we need to intervene in key pathways early in the disease. Osteoarthritis is characterised by loss of cartilage. Recent publications have indicated changes in the phenotype of cartilage cells (chondrocytes) before the tissue is damaged. We hypothesize that intervention in the pathway of these early changes in chondrocytes will prevent progression of osteoarthritis into a chronic disabling disease. With this partnership Erasmus MC and Galapagos will generate more knowledge on the phenotypical changes of chondrocytes during osteoarthritis using single cell RNA-seq. analyses of human cartilage. To obtain more insight in molecular processes that initiate these changes and in the progression of the phenotypical changes we will develop models to study whether and how vascularisation and inflammation (both occurring in early stages of osteoarthritis) are inducing or stimulating chondrocyte phenotypical changes. Finally, we will channel these results into creating a high throughput model to enable studies on molecular processes in the laboratory and to discover targets for the development of drugs for osteoarthritis. With globally >300 million patients and no available cure it can be foreseen that an effective intervention created using our model has the potential for rapid penetration in the market.