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Early Inflammatory Arthritis in the Rabbit: The Influence of Intraarticular and Systemic Corticosteroids on mRNA Levels in Connective Tissues of the Knee
ALISON S. KYDD, CAROL R. RENO, HELEN W. TSAO, and DAVID A. HART ABSTRACT. Objective. Using a rabbit model of inflammatory arthritis, to determine the influence of early disease on expression of specific genes and investigate the influence of intraarticular (IA) and intramuscular (IM) corticosteroids on the regulation of these genes in connective tissues of the rabbit knee. Methods. Skeletally mature rabbits underwent induction of antigen-induced arthritis or remained untreated as control animals. Four days after disease induction, at an early stage of the disease, animals underwent either IA or IM treatment with glucocorticoids (GC) (5 mg/knee and 10 mg/kg methylprednisolone acetate, respectively). Twenty-four hours following treatment, synovium, menisci, and cartilage of the knee were collected and analyzed for changes in mRNA levels using reverse transcription-polymerase chain reaction for a number of relevant genes: collagen I, collagen II, biglycan, decorin, matrix metalloproteinases-3 and -13 (MMP-3 and MMP-13), cyclooxygenases-1 and -2 (COX-1 and COX-2), tumor necrosis factor-a (TNF-a), interleukin 1ß (IL-1ß), inducible nitric oxide synthase (iNOS), hyaluronan synthase-2 (HAS-2), and the housekeeping gene ß-actin. Results. Early inflammatory arthritis led to an overall upregulation of most genes assessed, but a downregulation of some genes (iNOS, HAS-2, COX-1) in some tissues. While genes such as collagen II, MMP-3, and MMP-13 were uniformly downregulated by GC treatment in both normal and arthritic tissues, other genes such as collagen I, biglycan, and decorin differed in their pattern of response depending on the tissue examined, the route of drug administration, and whether normal or arthritic tissue was studied. Conclusion. Early mRNA changes in RA-like disease led to alterations in all tissues examined. The changes were uniquely altered by GC treatment. Route of GC administration influenced outcome. (First Release Nov 15 2006; J Rheumatol 2007;34:130–9) Key Indexing Terms:
GLUCOCORTICOIDS From the McCaig Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Supported by The Arthritis Society, The Institute for Gender and Health of the Canadian Institutes of Health Research, and the Alberta Bone and Joint Health Institute. ASK was supported by a Canadian Institutes of Health Research MD/PhD Studentship and is enrolled in the Leaders of Medicine program at the University of Calgary. A.S. Kydd, PhD; C.R. Reno; H.W. Tsao, BPharm; 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, Canada. E-mail: hartd@ucalgary.ca Accepted for publication August 27, 2006. |
