Wnt5a exacerbates pathological bone features and trabecular bone loss in curdlan-injected SKG mice via osteoclast activation.

Many studies on osteoblasts have suggested that Wnt5a plays a crucial role in excessive osteoblast activity, which is responsible for ectopic new bone formation, but research on osteoclasts in ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclast-mediated bone resorption in curdlan-injected SKG mice, a model that mimics AS. Compared to the Vehicle group, the Wnt5a treatment group exhibited statistically higher clinical arthritis scores and increased hindpaw thickness values. Micro-computed tomography (microCT) analysis of hindpaws revealed a significant increase in inflamed and ectopic bone density in the Wnt5a-treated group compared to the Vehicle group. Histological examination also showed pronounced inflammation and structural bone damage in the bone marrow of ankles in the Wnt5a-treated group. Intriguingly, microCT analysis of the femur revealed that trabecular bone loss was markedly observed in the Wnt5a-treated group. Both the number of TRAP-positive osteoclasts and their activity were statistically greater in the Wnt5a-treated group compared to the Vehicle group. Serum markers of bone resorption, but not bone formation, were also significantly elevated in the Wnt5a-treated group. Notably, promotion of osteoclast differentiation by Wnt5a was inhibited following treatment with anti-Wnt5a. These findings suggest that targeting Wnt5a could be a promising strategy for mitigating pathological bone features in AS by modulating osteoclast activity.