 |
|
|
 |
Influence of a Single Systemic Corticosteroid Injection on mRNA Levels for a Subset of Genes in Connective Tissues of the Rabbit Knee: A Comparison of Steroid Types and Effect of Skeletal Maturity
ALISON S. KYDD, CAROL RENO, JOVINA M. SORBETTI, and DAVID A. HART
ABSTRACT. Methods. Intraarticular and extraarticular connective tissues of the knee were collected from skeletally mature or immature rabbits at 72 and/or 24 h postinjection of a single intramuscular inoculation of 10 mg/kg methylprednisolone or dexamethasone (skeletally mature rabbits) or 1 mg/kg (skeletally immature rabbits). Total RNA was isolated and mRNA levels for matrix molecules, matrix metalloproteinases (MMP) and their inhibitors, cyclooxygenase-2, transforming growth factor-ß, glucocorticoid receptor, and heat shock protein 90 alpha and beta were assessed by RT-PCR. Results. Glucocorticoid treatment resulted in significant alterations in mRNA levels for a specific subset of genes in a tissue-specific and time-dependent manner in both maturity groups. Most notably, glucocorticoid treatment resulted in significant suppression of mRNA levels for collagens I and III, and MMP-3 and MMP-13. Conclusion. mRNA levels for both anabolic genes (collagens) and catabolic genes (MMP) in connective tissues are rapidly affected by systemic glucocorticoid treatment irrespective of skeletal maturity. This glucocorticoid sensitivity of normal tissues may lead to unwanted bystander effects when corticosteroids are used therapeutically, effects that could contribute to a negative influence on the functioning of such tissues. (J Rheumatol 2005;32:307-19) Key Indexing Terms:
GLUCOCORTICOIDS
From the McCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Supported by The Arthritis Society, National Institutes of Health (USA), Canadian Institutes for Health Research, and the National Science and Engineering Research Council (Canada). Ms Kydd was supported by a Canadian Institutes of Health Research MD/PhD Studentship. Ms Sorbetti was supported by a National Science and Engineering Research Council Summer Studentship. A.S. Kydd, BSc; C. Reno; J.M. Sorbetti, BSc; D.A. Hart, PhD, Calgary Foundation—Grace Glaum Professor in Arthritis Research, University of Calgary. Address reprint requests to Dr. D.A. Hart, McCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1. E-mail: hartd@ucalgary.ca Submitted December 3, 2003; revision accepted September 29, 2004. |