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). Sample Population - Articular cartilage specimens collected from 10 ponies, 2.5 to 3.5 years old and 200 to 300 kg. Procedure - 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. Clinical Relevance - 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.