Elucidating pathological mechanisms of joint degenerative disorders

Abstract

Joint degenerative disorders impose a large burden on lifestyle and the healthcare system. The goals of this thesis were to elucidate pathological mechanisms in osteoarthritis (OA) and juvenile osteochondritis dissecans (JOCD) in order to improve understanding of these diseases, and to provide well-characterized platforms for therapeutic development and testing. In order to bridge the gap in knowledge between preclinical and clinical studies, we characterized molecular events that occur in the rat medial meniscus transection model of post-traumatic OA as the disease develops and progresses. We then used this platform to investigate the mechanisms of action of micronized dehydrated human amnion/chorion membrane in order to elucidate potential disease-modifying mechanisms of this therapeutic. By utilizing cutting edge induced pluripotent stem cell technology, we established JOCD-specific models of chondrogenic and endochondral ossification differentiation, as well as endoplasmic reticulum-stress induction models. Our results shed light on pathological mechanisms of OA and JOCD and provided compelling data for the development of more targeted approaches for disease treatments.