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Effect of synovitis and corticosteroids on transcription of cartilage matrix proteins.

Abstract: 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.
Publication Date: 1998-08-26 PubMed ID: 9706207
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research study focused on how synovitis (inflammation of the synovial membrane often in arthritic conditions) and a corticosteroid (methylprednisolone acetate) influence the production of crucial cartilage proteins. These changes in protein production could have implications for the underlying processes of traumatic osteoarthritis and possible therapies.

Methods

  • The study used articular cartilage samples from 10 ponies aged 2.5 to 3.5 years and weighing between 200 to 300kg. The cartilage was test divided into four experimental groups for comparison: control, MPA-treated, lipopolysaccharide-induced synovitis, and lipopolysaccharide-induced synovitis with MPA treatment.
  • Researchers isolated the RNA from the articular cartilage and compared it through a process called Northern blot analysis, using equine-specific cDNA probes. Northern blot analysis is a technique used to detect specific RNA molecules among a mixture of RNA.

Results

  • Synovitis was observed to elevate the steady-state levels of type-II procollagen mRNA fivefold and aggrecan mRNA twofold. Both type-II procollagen and aggrecan are essential proteins for cartilage function and integrity.
  • A single dose of methylprednisolone acetate decreased the transcript levels of type-II procollagen in healthy cartilage sixfold, but didn’t significantly impact aggrecan or total fibronectin mRNA values. Fibronectin is another protein that helps to maintain the structure and function of cartilage.
  • For inflamed joints, MPA treatment returned the mRNA levels of type-II procollagen and aggrecan to near those of the untreated control samples.

Conclusions

  • The study concluded that in response to synovitis, articular chondrocytes (the cells producing cartilage) increase their production of type-II procollagen and aggrecan. This would appear to be a reaction aimed to maintain or restore the cartilage’s function and structure within the inflammatory environment of synovitis.
  • Methylprednisolone acetate was found to affect chondrocyte function in both healthy and inflamed cartilage, indicating it could influence protein synthesis. This outcome suggests that any changes in the synthesis of cartilage matrix proteins could be critical when evaluating the worth of corticosteroid treatments for joint-related disorders.
  • More extensive understanding of how synovitis and corticosteroids interact and affect cartilage protein synthesis could heighten our knowledge on the causes of traumatic osteoarthritis and aid to refine therapeutic strategies.

Cite This Article

APA
MacLeod JN, Fubini SL, Gu DN, Tetreault JW, Todhunter RJ. (1998). Effect of synovitis and corticosteroids on transcription of cartilage matrix proteins. Am J Vet Res, 59(8), 1021-1026.

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 59
Issue: 8
Pages: 1021-1026

Researcher Affiliations

MacLeod, J N
  • Department of Physiology, James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Fubini, S L
    Gu, D N
      Tetreault, J W
        Todhunter, R J

          MeSH Terms

          • Aggrecans
          • Animals
          • Cartilage, Articular / metabolism
          • Chondroitin Sulfate Proteoglycans / genetics
          • Escherichia coli
          • Extracellular Matrix Proteins / biosynthesis
          • Extracellular Matrix Proteins / genetics
          • Female
          • Fibronectins / genetics
          • Glucocorticoids / therapeutic use
          • Horse Diseases / chemically induced
          • Horse Diseases / drug therapy
          • Horse Diseases / metabolism
          • Horses
          • Lectins, C-Type
          • Lipopolysaccharides
          • Male
          • Methylprednisolone / therapeutic use
          • Orchiectomy
          • Procollagen / genetics
          • Proteoglycans / genetics
          • RNA, Messenger / metabolism
          • Synovitis / chemically induced
          • Synovitis / drug therapy
          • Synovitis / metabolism
          • Synovitis / veterinary
          • Transcription, Genetic / drug effects

          Citations

          This article has been cited 3 times.