Lessons from animal models of osteoarthritis.
Characterization of transgenic murine osteoarthritis (OA) models and analysis of anterior cruciate ligament and meniscectomy models in various species, including rodents, has provided insight into pathogenic mechanisms and impact of loading. Development of a transgenic murine OA model by postnatal expression in hyaline cartilage of constitutively expressed human matrix metalloproteinase-13 emphasizes the potential role of this enzyme. On the other hand, collagenase involvement in OA models seems a confined focal process, complicating therapeutic approaches. The potential role of interleukin-1 still needs further confirmation. Apart from destructive cytokines, disturbed growth factor responses seems obvious. Transforming growth factor-beta is a crucial mediator in osteophyte formation, but its role in cartilage destruction has not yet been clarified. Nitric oxide appears involved in chondrocyte apoptosis and blocking of nitric oxide provides protection against joint pathology in OA models. Treatment with a range of disease-modifying drugs showed some efficacy in a number of OA models, but its predictive value for human OA remains obscure.
van den Berg
W B
WB
Rheumatology Research and Advanced Therapeutics, University Medical Center, Nijmegen Geert Grooteplein 26-28 6500 HB, Nijmegen, The Netherlands. w.vandenberg@reuma.azn.nl
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002358:Cartilage, Articular / Q000201:enzymology / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D006133:Growth Substances / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D011817:Rabbits; D016474:Weight-Bearing
D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D006133:Growth Substances; D009569:Nitric Oxide; D003094:Collagen; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse