Intra-articular VEGF inhibition attenuates cartilage degeneration in a rat model of post-traumatic osteoarthritis: a...

Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degeneration, subchondral bone remodelling, and pathological synovial changes. Vascular endothelial growth factor (VEGF) plays a central role in the neovascularization that drives OA pathophysiology, making VEGF blockade a candidate disease-modifying strategy. To evaluate the histopathological effects of intra-articular bevacizumab, a VEGF inhibitor, on cartilage integrity in a surgically induced rat model of post-traumatic osteoarthritis. Post-traumatic OA was induced by creating full-thickness osteochondral defects in the medial femoral condyles of Wistar albino rats. As both hind limbs were used, individual joints served as the unit of histological analysis. Joints were allocated to four groups: sham (n = 2 joints), OA control (n = 8 joints), bevacizumab 1.25 mg/mL (n = 7 joints), and bevacizumab 2.5 mg/mL (n = 4 joints). Group sizes were unequal owing to tissue loss during histological processing. Bevacizumab (Avastin^®, Roche) or saline was administered intra-articularly (50 µL per joint, 30-gauge needle) immediately after surgery and repeated at postoperative weeks 2 and 4. Joints were harvested at week 8 and evaluated histologically using haematoxylin-eosin and toluidine blue staining. Cartilage degeneration was graded using the OARSI semiquantitative scoring system. Group differences were assessed using the Kruskal-Wallis test with post-hoc Mann-Whitney U comparisons. Due to the small and unequal group sizes, this study was conducted as a pilot investigation. Effect sizes for all pairwise comparisons were large (r = 0.648-0.776). All animals tolerated the procedures without systemic complications. OA control joints demonstrated marked cartilage surface damage, chondrocyte clustering, proteoglycan loss, and synovial changes. OARSI scores were significantly higher in the OA control group (median 10.5, IQR 6.0-15.0) compared with the bevacizumab 1.25 mg/mL group (median 2.0, IQR 2.0-5.0; p = 0.008) and the bevacizumab 2.5 mg/mL group (median 0.0, IQR 0.0-0.25; p = 0.007). A significant difference was also observed between the two bevacizumab doses (p = 0.032). Overall group comparison was significant (Kruskal-Wallis H = 12.90, p = 0.0016). Sham joints (n = 2 joints) showed minimal degenerative changes and were not included in formal statistical comparisons. Intra-articular bevacizumab attenuated cartilage degeneration in a dose-dependent manner in this pilot rat model of post-traumatic OA. These preliminary findings support the hypothesis that VEGF inhibition may confer chondroprotective effects and warrant confirmation in larger, adequately powered studies using established OA models with molecular endpoint assessment.