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

초록

Many studies on osteoblasts have suggested that Wnt5a plays a crucial role in excessive osteoblast activity, which is res-ponsible for ectopic new bone formation, but research on oste-oclasts 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. His-tological 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. [BMB Reports 2025; 58(2): 75-81]

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