Characterizing osteochondrosis in the dog: potential roles for matrix metalloproteinases and mechanical load in pathogenesis and disease progression

Osteoarthritis Cartilage. 2005 Mar;13(3):225-34. doi: 10.1016/j.joca.2004.11.005.

Abstract

Objective: To address possible roles of matrix metalloproteinases (MMPs) and mechanical stress in the pathogenesis of osteochondrosis (OC).

Methods: Naturally-occurring canine OC lesions (n=50) were immunohistochemically analyzed for MMP-1, -3, and -13, and normal canine articular cartilage explants (n=6) cultured under 0-, 2-, or 4-MPa compressive loads (0.1 Hz, 20 min every 8 h up to 12 days) were compared to OC samples (n=4) biochemically and molecularly.

Results: MMP-1 and -3 immunoreactivities were readily detected in both OC samples and control tissues obtained from age-matched dogs (n=11) whereas MMP-13 was only detectable in OC samples. MMP-13 gene expression as determined by real-time reverse transcription polymerase chain reaction was elevated in OC samples and cartilage explants cultured without mechanical stimuli (0 MPa groups) compared to normal cartilage (day 0 controls). Glycosaminoglycan content (per weight) in cartilage explants cultured under no load was significantly (P<0.05) lower on day 12 than in the day 0 controls. Gene expression levels of aggrecan and type II collagen in OC samples were lower than those in the day 0 controls. High levels of aggrecan and collagen II expression were seen in the 2 MPa groups.

Conclusions: These findings imply that impaired biochemical characteristics in OC-affected cartilage may be attributable to decreased extracellular matrix production that may stem from disruption of normal weight bearing forces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / physiology
  • Cell Survival
  • Chondrocytes / physiology
  • Disease Progression
  • Dog Diseases / enzymology
  • Dog Diseases / etiology*
  • Dogs
  • Extracellular Matrix / metabolism
  • Gene Expression
  • Glycosaminoglycans / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Matrix Metalloproteinases / physiology*
  • Osteochondritis / enzymology
  • Osteochondritis / etiology*
  • Osteochondritis / veterinary*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Stress, Mechanical
  • Tissue Culture Techniques
  • Weight-Bearing

Substances

  • Glycosaminoglycans
  • Matrix Metalloproteinases