title: Characterizing osteochondrosis in the dog: potential roles for matrix metalloproteinases and mechanical load in pathogenesis and disease progression.
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.
authors.affiliation: Comparative Orthopaedic Laboratory, University of Missouri, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kuroki
authors.forename: J L
authors.initials: JL
authors.lastname: Cook
authors.forename: A M
authors.initials: AM
authors.lastname: Stoker
authors.forename: S E
authors.initials: SE
authors.lastname: Turnquist
authors.forename: J M
authors.initials: JM
authors.lastname: Kreeger
authors.forename: J L
authors.initials: JL
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000502:physiology; D002470:Cell Survival; D019902:Chondrocytes / Q000502:physiology; D018450:Disease Progression; D004283:Dog Diseases / Q000201:enzymology / Q000209:etiology*; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D006025:Glycosaminoglycans / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010007:Osteochondritis / Q000201:enzymology / Q000209:etiology* / Q000662:veterinary*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013314:Stress, Mechanical; D046509:Tissue Culture Techniques; D016474:Weight-Bearing
chemical_list: D006025:Glycosaminoglycans; D020782:Matrix Metalloproteinases