(Georgia Institute of Technology, 2019-05)
Nations, Catriana C.
The application of pluripotent stem-cell based in vitro models has become increasingly popular in medical research, especially for situations in which animal modeling is not sufficient to accurately describe the condition or for diseases where there is little research demonstrating the relationships between disease phenotype, pathological cellular mechanisms, and gene expression. Such is the case with Juvenile Osteochondritis Dissecans (JOCD), a degenerative bone disease that predominately affects the knee joints of children and progresses to early onset osteoarthritis. Previous research has involved the use of animal models or diseases similar to JOCD, but there has been little to no focus on the cellular mechanisms of this condition. Therefore, this study aimed to elucidate the cellular pathophysiology of JOCD as well as provide a test bed for future therapeutic interventions. We hypothesized that our iPSC in vitro models of JOCD would show protein dysfunction and accumulation in the rough endoplasmic reticulum as a hallmark of the disease, as previously shown in familial and equine OCD.