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

• Published in: Osteoarthritis and cartilage Vol. 13; no. 3; pp. 225 - 234
• Main Authors: Kuroki, K., Cook, J.L., Stoker, A.M., Turnquist, S.E., Kreeger, J.M., Tomlinson, J.L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2005
• Subjects: Animals; Cartilage, Articular - metabolism; Cartilage, Articular - physiology; Cell Survival; Chondrocytes - physiology; Compressive load; Disease Progression; Dog; Dog Diseases - enzymology; Dog Diseases - etiology; Dogs; Extracellular Matrix - metabolism; Gene Expression; Glycosaminoglycans - metabolism; Matrix metalloproteinase; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Matrix Metalloproteinases - physiology; Osteoarthritis; Osteochondritis - enzymology; Osteochondritis - etiology; Osteochondritis - veterinary; Reverse Transcriptase Polymerase Chain Reaction - methods; Stress, Mechanical; Tissue Culture Techniques; Weight-Bearing; Matrix metalloproteinase; Osteoarthritis; Compressive load; Dog
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2004.11.005

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