Background Osteoarthritis (OA) is the most prevalent form of arthritis in EU countries and is characterised by cartilage degeneration, subchondral bone thickening and synovial inflammation. However, the molecular mechanisms involved in initiation and progression of the disease are poorly understood. A recent study suggested that vascular endothelial growth factor (VEGF) is re-expressed in osteoarthritic cartilage in guinea pigs1, therefore it is conceivable that VEGF plays an important role in the molecular mechanisms leading to cartilage damage and/or bone remodelling.
Objectives The aims of the present study are to identify changes in the proportions of VEGF positive chondrocytes in the articular cartilage of Dunkin-Hartley (DH) guinea pigs during aging, development and progression of OA. In addition, the relationship between VEGF expression and various parameters of bone and cartilage remodelling will be investigated.
Methods Male DH guinea pigs are known to develop spontaneous OA first on the medial side and later on the lateral side of the knee joint by the age of 8 - 12 weeks2. The animals were sacrificed at ages 10 (n=6), 16 (n=6), 24 (n=4) and 30 (n=4) weeks and weighed. Their right tibias were harvested and snap frozen in cold isopentane with articular cartilage intact then 7μm sections of the whole joint were taken using a specially adapted cryostat. Indirect immunohistochemistry was used to detect the isoform VEGF-165 A (R&D systems) followed by a Carazzi's haematoxylin counterstain.
At each time point bone mineral density (BMD) was measured using dual X-ray absorptiometry, subchondral bone plate thickness (SbpTh) was obtained using micro-computed tomography imaging, and cartilage thickness (CTh) was measured directly by light microscopy. The proportions of VEGF positive cells were then correlated to BMD, SbpTh, maximum CTh and bodyweight across each age group.
Results A Mann-Whitney U test revealed the proportion of VEGF-positive cells was significantly higher at 10 weeks than at 30 weeks (mean % ± SD: 45±18 vs. 20±8 vs. p=0.021). Comparison of VEGF expression in the medial and lateral sides shows that by 30 weeks there is greater expression of VEGF in the medial side. SbpTh (p=0.001) and bodyweight (p=0.001) increased significantly with age as would be expected during normal growth. Spearman's Rho correlation analysis identified marginally significant relationships between VEGF-positive cells and BMD (r=-0.424, p=0.062).
Conclusions The data show that the expression of VEGF in chondrocytes decreases from 10 to 30 weeks in DH guinea pigs, and at 30 weeks there is greater VEGF expression on the medial side of the joint when all animals had established OA. These results contrast with those of a previous study in that VEGF positive chondrocytes were found at all ages. Our data suggest that VEGF is involved in OA as well as normal growth, and further studies using a suitable control animal and other isoforms of VEGF would improve our understanding of the molecular mechanisms in OA.
Lingaraj et al 2010. Vascular endothelial growth factor (VEGF) is expressed during articular cartilage growth and re-expressed in osteoarthritis. Ann Acad Med Singapore; 39:399-403.
Kraus et al 2010. The OARSI Histopathology Initiative - Recommendations for Histological Assessment of Osteoarthritis in the Guinea Pig. OA Cart; 18: 35-52.
Disclosure of Interest : None declared
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