The impact of glucocorticoids on connective tissues
Date
2006
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Glucocorticoids are widely used in the treatment of orthopaedic and rheumatologic conditions such as joint injury and mihritis. Despite their widespread use, there is little understanding of the mechanisms by which gl ucocorticoids affect connective tissues and the impact that this has on injury and disease processes. The research presented in this dissertation represents an examination of the impact of glucocorticoids on connective tissues and how the response of these tissues is altered in situations of injury, inflammation, and degeneration. By characterizing the response of connective tissues both directly involved in joint pathologies and those indirectly affected, these studies offer a unique insight into the complex interactions between interdependent connective tissues and systemic factors such as the inflammatory and stress responses. The major findings of this dissertation are as follows: First, normal connective tissues of the rabbit knee, including ligaments, meniscus, synovium and cartilage are responsive to glucocorticoid treatment, but this responsiveness often exhibits tissue- and gene-specific regulation. Second, while connective tissues were responsive to glucocorticoid treatment, the impact that these drugs have on these tissues is depenedent on the route by which glucocorticoids are administered, with intra-articular administration leading to more significant alterations in mRNA levels than intra-muscular treatment. Third, glucocorticoid-mediated gene responsiveness is paradoxically altered in the context of tissue injury, joint inflammation and in ancillary suppo1i tissues of unstable joints. Fourth, ACL-transection and the joint degeneration associated with it impart gene transcript changes in distant connective tissues such as the cornea. Finally, the AP-1 promoter element likely plays a role in glucocorticoid-mediated transcriptional regulation of a subset of genes highly relevant to connective tissue homeostasis and remodelling. These studies indicate that clinically, glucocorticoids treatment likely affects connective tissues of the joint but that this impact is not uniform in nature, resulting in a different pattern of response depending on the tissue, the timing of the treatment, and the presence of injury, inflammation and tissue adaptation. Further study of these glucocorticoid-mediated responses will more clearly elucidate the tissue and disease response to glucocorticoids and provide a knowledge framework on which to better determine the risks and benefits of clinical glucocorticoid interventions.
Description
Bibliography: p. 193-226
Keywords
Citation
Kydd, A. S. (2006). The impact of glucocorticoids on connective tissues (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4805