High Resolution Imaging Of Early, Subclinical Cartilage Injuries: Implications For The Diagnosis And Treatment Of Post-Traumatic Osteoarthritis

Abstract

Osteoarthritis (OA) is a degenerative disease. Currently, there are no treatments to restore damaged cartilage to its native state. Joint injury increases the risk of developing post-traumatic OA (PTOA). Subtle cartilage injury that may progress to PTOA cannot be detected with current clinical imaging modalities. If subtle cartilage injury is detectable, PTOA can be better understood to develop treatments targeting early disease progression. The goal of this dissertation was to evaluate methods for detecting, characterizing, and treating early cartilage injury. Multiphoton microscopy (MPM) can provide high resolution details of live, intact tissue. The purpose of the first study was to validate the use of MPM to detect subtle cartilage damage. The results confirmed the ability of MPM to resolve structural changes and cell death in cartilage immediately after injury. This suggests future application of MPM in the clinic for early diagnosis or in the laboratory to perform longitudinal studies not currently possible due to the necessity of histological processing. In the second study, cartilage and its resiliency to injury were evaluated among eight major joints to determine if there are different susceptibilities to injury in different joints. The structure of articular cartilage and prevalence of OA vary among joints, but typically results from work performed within a single joint are applied to other joints. The results from the second study showed that some joints have more cellular death and/or decrease anabolic gene expression than other joints after receiving the same injury, which suggests the need for joint specific treatments. The third study examined the role of oxygen in the development of PTOA. Cartilage is avascular and has limited oxygen supply. Oxygen tension may be increased in arthritic joints, yet short exposure to high oxygen tension is beneficial to uninjured cartilage. In this final study, the effect of increased oxygen tension on cartilage viability after injury was evaluated. The immediate application of hyperoxic treatment minimized cell death after injury, suggesting that the immediate application of high oxygen following injury may be chondroprotective. These findings have implications in future treatments that could minimize the effect of cartilage injury and development of PTOA