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.
OBJECTIVE
. To determine the effect of glucocorticoid treatment on mRNA levels for matrix molecules and enzymes in knee connective tissues from skeletally mature and skeletally immature rabbits.


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.


CONCLUSIONS
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.
Kydd
Alison S
AS
McCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Reno
Carol
C
Sorbetti
Jovina M
JM
Hart
David A
DA
D000375:Aging; D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007273:Injections, Intramuscular; D008023:Ligaments, Articular / Q000187:drug effects* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013264:Stifle / Q000187:drug effects* / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases; D008775:Methylprednisolone