Effect of synovitis and corticosteroids on transcription of cartilage matrix proteins.
OBJECTIVE
To determine whether steady-state levels of type-II procollagen, aggrecan core protein, or fibronectin mRNA in articular chondrocytes are altered by synovitis or administration of methylprednisolone acetate (MPA).


METHODS
Articular cartilage specimens collected from 10 ponies, 2.5 to 3.5 years old and 200 to 300 kg.


METHODS
4 experimental groups were compared, using the cartilage specimens: control, MPA-treated, lipopolysaccharide-induced synovitis, and lipopolysaccharide-induced synovitis with MPA treatment. RNA was isolated from articular cartilage and compared by northern blot analysis, using equine-specific cDNA probes.


RESULTS
Synovitis increased steady-state levels of type-II procollagen mRNA fivefold and of aggrecan mRNA twofold. Administration of a single intra-articular injection of MPA (0.1 mg/kg of body weight) decreased type-II procollagen transcripts in normal cartilage sixfold, without significant effect on aggrecan or total fibronectin mRNA values. MPA treatment of inflamed joints decreased type-II procollagen and aggrecan mRNA to levels that were not significantly different from those in untreated control specimens.


CONCLUSIONS
Articular chondrocytes increase type-II procollagen and aggrecan synthesis in response to synovitis. MPA alters chondrocyte function in normal and inflamed cartilage, suggesting that potential changes in cartilage matrix protein synthesis should be considered when evaluating the therapeutic value of intra-articular administration of corticosteroids.


CONCLUSIONS
Knowledge of how synovitis and corticosteroids (independently and in combination) affect synthesis of cartilage matrix proteins is relevant to understanding pathogenesis of traumatic osteoarthritis and improving therapeutic strategies.
Department of Physiology, James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J N
JN
MacLeod
S L
SL
Fubini
D N
DN
Gu
J W
JW
Tetreault
R J
RJ
Todhunter
D053674:Aggrecans; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D004926:Escherichia coli; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005353:Fibronectins / Q000235:genetics; D005938:Glucocorticoids / Q000627:therapeutic use*; D006734:Horse Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D006736:Horses; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D009919:Orchiectomy; D011347:Procollagen / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013585:Synovitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D014158:Transcription, Genetic / Q000187:drug effects
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005938:Glucocorticoids; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011347:Procollagen; D011509:Proteoglycans; D012333:RNA, Messenger; D008775:Methylprednisolone