Whangbo Min, Ko Eunae, Kim Dongju, Jeon Chanhyeok, Jo Hye-Ryeong, Lee Seung Hoon, Youn Jeehee, Jo Sungsin, Kim Tae-Hwan
Hanyang University Institute for Rheumatology Research (HYIRR), Seoul 04763; Department of Translational Medicine Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea.
Hanyang University Institute for Rheumatology Research (HYIRR), Seoul 04763, Korea.
BMB Rep. 2025 Feb;58(2):75-81. doi: 10.5483/BMBRep.2024-0155.
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 osteoclastmediated 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. [BMB Reports 2025; 58(2): 75-81].
许多关于成骨细胞的研究表明，Wnt5a在成骨细胞过度活跃中起关键作用，而成骨细胞过度活跃会导致异位新骨形成，但关于强直性脊柱炎（AS）破骨细胞的研究仍然相对有限。本研究旨在探讨Wnt5a是否会影响注射了可德兰的SKG小鼠（一种模拟AS的模型）中破骨细胞介导的骨吸收。与载体组相比，Wnt5a治疗组的临床关节炎评分在统计学上更高，后足厚度值增加。对后足进行的显微计算机断层扫描（microCT）分析显示，与载体组相比，Wnt5a治疗组的炎症骨密度和异位骨密度显著增加。组织学检查还显示，Wnt5a治疗组踝关节骨髓中有明显的炎症和结构性骨损伤。有趣的是，对股骨进行的microCT分析显示，Wnt5a治疗组明显观察到小梁骨丢失。与载体组相比，Wnt5a治疗组中抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞的数量及其活性在统计学上都更高。Wnt5a治疗组中骨吸收的血清标志物（而非骨形成的血清标志物）也显著升高。值得注意的是，用抗Wnt5a治疗后，Wnt5a对破骨细胞分化的促进作用受到抑制。这些发现表明，靶向Wnt5a可能是一种通过调节破骨细胞活性来减轻AS病理骨特征的有前景的策略。[《BMB报告》2025年；58(2): 75 - 81]
