Wnt5a exacerbates pathological bone features and trabecular bone loss in curdlan-injected SKG mice via osteoclast activation
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Many studies on osteoblasts have suggested that Wnt5a playsa crucial role in excessive osteoblast activity, which is responsiblefor ectopic new bone formation, but research on osteoclastsin ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclastmediatedbone resorption in curdlan-injected SKG mice, amodel that mimics AS. Compared to the Vehicle group, theWnt5a treatment group exhibited statistically higher clinicalarthritis scores and increased hindpaw thickness values. Micro–computed tomography (microCT) analysis of hindpaws revealeda significant increase in inflamed and ectopic bone density inthe Wnt5a-treated group compared to the Vehicle group. Histologicalexamination also showed pronounced inflammationand structural bone damage in the bone marrow of ankles inthe Wnt5a-treated group. Intriguingly, microCT analysis of thefemur revealed that trabecular bone loss was markedly observedin the Wnt5a-treated group. Both the number of TRAP-positiveosteoclasts and their activity were statistically greater in theWnt5a-treated group compared to the Vehicle group. Serummarkers of bone resorption, but not bone formation, were alsosignificantly elevated in the Wnt5a-treated group. Notably,promotion of osteoclast differentiation by Wnt5a was inhibitedfollowing treatment with anti-Wnt5a. These findings suggestthat targeting Wnt5a could be a promising strategy for mitigating pathological bone features in AS by modulating osteoclast activity.
Abstract
Many studies on osteoblasts have suggested that Wnt5a playsa crucial role in excessive osteoblast activity, which is responsiblefor ectopic new bone formation, but research on osteoclastsin ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclastmediatedbone resorption in curdlan-injected SKG mice, amodel that mimics AS. Compared to the Vehicle group, theWnt5a treatment group exhibited statistically higher clinicalarthritis scores and increased hindpaw thickness values. Micro–computed tomography (microCT) analysis of hindpaws revealeda significant increase in inflamed and ectopic bone density inthe Wnt5a-treated group compared to the Vehicle group. Histologicalexamination also showed pronounced inflammationand structural bone damage in the bone marrow of ankles inthe Wnt5a-treated group. Intriguingly, microCT analysis of thefemur revealed that trabecular bone loss was markedly observedin the Wnt5a-treated group. Both the number of TRAP-positiveosteoclasts and their activity were statistically greater in theWnt5a-treated group compared to the Vehicle group. Serummarkers of bone resorption, but not bone formation, were alsosignificantly elevated in the Wnt5a-treated group. Notably,promotion of osteoclast differentiation by Wnt5a was inhibitedfollowing treatment with anti-Wnt5a. These findings suggestthat targeting Wnt5a could be a promising strategy for mitigating pathological bone features in AS by modulating osteoclast activity.