Cellular Senescence as a driver and therapeutic target for osteoarthritis (OA)

The search for disease-modifying drugs for osteoarthritis has been very challenging, and many patients have to withstand high levels of pain until the time is right for a total joint replacement. Increased age-related dysfunction of the cells inside cartilage, called chondrocytes, is believed to be a key driver in the development of osteoarthritis. Dr. Diekman and his team are using engineered tissues and animal models to investigate precisely why these cells become dysfunctional with age. They are looking specifically at cellular senescence, a phenomenon by which normal diploid cells (cells with two sets of chromosomes) are unable to divide. Cellular senescence is characterized in part by the secretion of pro-inflammatory molecules that may harm surrounding healthy cells. One strategy to improve tissue function with age is to deliver 'senolytic' compounds that specifically kill senescent cells and prevent the secretion of these molecules. Dr. Diekman is working to determine the functional role of cellular senescence in osteoarthritis and to test senolytics for the ability to target chondrocytes. He will also test senolytic compounds for their ability to prevent age-related osteoarthritis through periodic treatment. These experiments will examine whether senolytic drugs should be explored as a potential class of disease-modifying osteoarthritis drugs.