作者: Rosalind M. Hembry , Jonathan Dyce , Iris Driesang , Ernst B. Hunziker , Amanda J. Fosang
DOI: 10.2106/00004623-200106000-00003
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摘要: Background: Partial-thickness defects in mature articular cartilage do not heal spontaneously. Attempts at repair often result limited integration between the tissue and surrounding cartilage, with formation of chondrocyte clusters adjacent to a zone necrosis. In wound repair, spatially temporally controlled expression matrix metalloproteinases their inhibitors have been implicated proteolytic degradation damaged extracellular components, but sequence events following damage is unknown. To determine this sequence, we studied distribution during early vivo partial-thickness pig cartilage. Methods: With use model that elicits ingrowth mesenchymal cells into defects, were created knee joint cartilage. The distributions metalloproteinase-1, 2, 3, 9, 13, 14; metalloproteinase-1 2; neoepitope DIPEN341 specifically generated metalloproteinase cleavage aggrecan determined by immunolocalization excised from immature pigs first eight weeks adult minipigs days three weeks. Results: Synthesis metalloproteinase-13 was usually confined hypertrophic chondrocytes radial Following injury, strong induction synthesis observed lesions all animals. migration macrophages prominent two days, deposition metalloproteinase-9 onto newly synthesized defect. localized six weeks, indicating partial aggrecan. Focal 14 inhibitor occurred later times, suggesting continuous remodeling increasingly compact tissue. Conclusions: normal necrosis suggest enzyme participates pericellular proteolysis required for lacunar expansion. localization suggested proteolysis, which confirmed localization. Reduced metachromasia persisted colocalized weeks. However, under conditions investigated, there only This may render mechanically weakened, thereby contributing subsequent instability region, form barrier viable cartilage. Clinical Relevance: Osteoarthritis initially involves superficial layers development procedures promote healing or will major advantages terms disease alleviation as well economic importance. Identification enzymes involved clinically relevant because has take place order integrate healthy