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<p>The trapping of pathogenic ligands can potentially be used to prevent signal transduction mediated by catabolic factor expression in osteoarthritis (OA). Although vaspin is known to function as a pathogenic ligand and represents a novel adipokine, little is known about its function and the impact of its nebulization-based administration in OA. Here we provide a report on the function of vaspin in articular chondrocytes and OA model mice. RNA sequencing analysis and ingenuity pathway analysis demonstrated that vaspin upregulation in chondrocytes triggers OA development-related signaling. Vaspin is upregulated in the injured cartilage of patients with OA and DMM (Destabilization of the Medial Meniscus) mice, and its overexpression induces catabolic factor expression in vitro under OA-mimicked conditions. Col2a1–vaspin Tg (Transgenic) animals showed extensive cartilage degradation, whereas vaspin<sup>−/−</sup> (knockout) mice exhibited decreased OA development. Furthermore, in silico and biochemical analyses showed that vaspin activates the p38 and JNK signaling pathways to regulate AP-1-driven catabolic factor production and cartilage breakdown. Finally, we identified and characterized a vaspin-targeting nanobody, vas nanobody, and showed that intraarticularly injected vas nanobody could effectively block the vaspin–AP-1 axis to treat OA in DMM mice. Together, our results suggest that blockade of the vaspin–AP-1 axis could be an effective therapeutic approach for preventing OA development.</p>

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Blockade of the vaspin–AP-1 axis inhibits arthritis development

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月3日

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  • Jimin Jeon,
  • Chanmi Cho,
  • Seoyeong Kim,
  • Hyeran Kim,
  • Hyemi Lee,
  • Seok Jung Kim,
  • Hwangseo Park,
  • Ji Hoon Yu,
  • Sangho Lee,
  • Kyu-Sun Lee,
  • Juyeon Jung,
  • Siyoung Yang

摘要

The trapping of pathogenic ligands can potentially be used to prevent signal transduction mediated by catabolic factor expression in osteoarthritis (OA). Although vaspin is known to function as a pathogenic ligand and represents a novel adipokine, little is known about its function and the impact of its nebulization-based administration in OA. Here we provide a report on the function of vaspin in articular chondrocytes and OA model mice. RNA sequencing analysis and ingenuity pathway analysis demonstrated that vaspin upregulation in chondrocytes triggers OA development-related signaling. Vaspin is upregulated in the injured cartilage of patients with OA and DMM (Destabilization of the Medial Meniscus) mice, and its overexpression induces catabolic factor expression in vitro under OA-mimicked conditions. Col2a1–vaspin Tg (Transgenic) animals showed extensive cartilage degradation, whereas vaspin−/− (knockout) mice exhibited decreased OA development. Furthermore, in silico and biochemical analyses showed that vaspin activates the p38 and JNK signaling pathways to regulate AP-1-driven catabolic factor production and cartilage breakdown. Finally, we identified and characterized a vaspin-targeting nanobody, vas nanobody, and showed that intraarticularly injected vas nanobody could effectively block the vaspin–AP-1 axis to treat OA in DMM mice. Together, our results suggest that blockade of the vaspin–AP-1 axis could be an effective therapeutic approach for preventing OA development.