Early inflammatory arthritis in the rabbit: the influence of intraarticular and systemic corticosteroids on mRNA levels in connective tissues of the knee.
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-alpha (TNF-alpha), interleukin 1beta (IL-1beta), inducible nitric oxide synthase (iNOS), hyaluronan synthase-2 (HAS-2), and the housekeeping gene beta-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.


CONCLUSIONS
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.
Kydd
Alison S
AS
McCaig Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Reno
Carol R
CR
Tsao
Helen W
HW
Hart
David A
DA
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007270:Injections, Intra-Articular; D007273:Injections, Intramuscular; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000199:Actins; D000305:Adrenal Cortex Hormones; D053583:Interleukin-1beta; D011509:Proteoglycans; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases