Changes in the antiangiogenic properties of articular cartilage in osteoarthritis.
Avascularity is important for the unique biomechanical properties of articular cartilage, and normal cartilage actively repels vascular invasion. This study investigated whether the antiangiogenic properties changed in the presence of osteoarthritis (OA) by culturing explants of human articular cartilage on the chorioallantoic membrane (CAM) of chick embryos and investigating the incidence of vascular invasion and the effects of exogenous vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). The results were compared with those of non-OA cartilage obtained after femoral neck fractures. Altogether, 72% of OA samples but only 5% of non-OA samples were invaded by the CAM, indicating that changes in the antiangiogenic properties represented a fundamental difference between control and OA cartilage. Exogenous VEGF or MMP-9 increased the frequency of invasion to 70%-100%. Invasion most frequently occurred into cartilage matrix from which proteoglycans had been lost, the latter being detectable by sirius red staining of cartilage collagen. VEGF was synthesized by chondrocytes in proportion to the severity of degradation and might exacerbate the loss of resistance to invasion. These results indicate that loss of resistance to vascular invasion distinguishes OA cartilage from normal articular cartilage, which may be important in the pathogenesis of OA.
Smith
James O
JO
University Orthopaedics, University of Southampton, CF86, Southampton General Hospital, Southampton SO16 6YD, UK.
Oreffo
Richard O C
RO
Clarke
Nicholas M P
NM
Roach
Helmtrud I
HI
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002358:Cartilage, Articular / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D003470:Culture Media; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism* / Q000494:pharmacology; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D003470:Culture Media; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9