Monoclonal Antibodies Against Vascular Endothelial Growth Factor A (VEGF-A) Reduce Synovitis, Bone Damage, and Osteogenesis in an SKG Mouse Model of Spondyloarthritis.

Abstract

Vascular endothelial growth factor-A (VEGF-A) plays a pivotal role in inflammatory rheumatic diseases, including spondyloarthritis (SpA). Recently, we have demonstrated that the expression of VEGF-A in human classical monocytes is positively associated with the number of swollen and painful joints in SpA patients. Therefore, we tested whether the anti-VEGF-A therapy can affect the hallmarks of SpA in the SKG mouse model. When initiated at the disease onset, the administration of anti-VEGF-A monoclonal antibodies (mAbs) significantly reduced the objective symptoms of SpA in the curdlan suspension-treated mice compared to their untreated and isotypic control-treated counterparts. Micro-computed tomography (CT) imaging revealed substantial benefits of the treatment, with anti-VEGF-A mAbs-treated mice exhibiting preserved joint spaces, reduced number and depth of bone erosions, and limited new bone formation in hind paws, calcaneus, sacroiliac joints, and caudal vertebrae. These effects remained in contrast to the pronounced damage and osteogenesis in relevant skeletal regions of control animals. The histological assessment confirmed reduced synovial inflammation and bone erosions in anti-VEGF-A mAbs-treated mice, underscoring the efficacy of the treatment in mitigating SpA bone damage. Collectively, anti-VEGF-A mAbs treatment favors the maintenance of joint and spine structures, alleviates bone destruction and osteogenesis, and reduces local inflammation in the mouse SpA model. Our study pinpoints anti-VEGF-A mAb therapy as a promising avenue to understand the SpA pathogenesis and as a treatment option. It also addresses vascular and inflammatory aspects of the disease and illustrates the potential of the SKG mouse SpA model for assessing the long-term safety of anti-VEGF-A therapy before its clinical translation.