A novel rat osteoarthrosis model to assess apoptosis and matrix degradation.
Matrix degradation and apoptosis are two crucial features of osteoarthrosis (OA), but the relationship between them needs to be clarified. We developed a novel OA model in partial meniscectomisized rats for the assessment in situ of these processes. The surgical procedure used permitted us to identify and remove 30-50% of the meniscus. Furthermore, the inclusion of high impact exercise enhanced the cartilage damage in a short period of time. OA cartilage displayed a rough and eroded surface, fibrosis and even complete loss; we also found hypertrophy, chondrocyte clusters and a disrupted extracellular matrix. As evidence of matrix degradation we found a diminution of the extracellular components such as chondroitin sulfate-4, 6 (CS-4, 6) and proteoglycans (PGs), and an overall increased activity of the PGs-degrading enzyme, stromelysin-1 (SLN-1). Moreover, the frequency of apoptotic chondrocytes increased according to the severity of the matrix degradation, as detected by TUNEL technique and by morphology. All these changes were enhanced in OA rats with high-impact exercise. Trained rats showed a statistically highly significant difference in histological changes compared to untrained animals. We demonstrate that our model can be evaluated according to Mankin's histologically graded parameters. Also, it is an effective method to assess, in situ, apoptosis in an experimentally induced OA. Our results suggest that apoptosis could be involved in matrix degradation and that TUNEL might be a good method for spotting early apoptotic changes which, combined with careful morphological examinations, provide substantial help in improving apoptosis detection.
Lozoya
K A
KA
Departamento de Patología Experimental, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), México D.F., México.
Flores
J B
JB
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D002809:Chondroitin Sulfates / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018613:Microscopy, Confocal; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010805:Physical Conditioning, Animal; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D011509:Proteoglycans; D002809:Chondroitin Sulfates; D019278:Matrix Metalloproteinase 3