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

Abstract

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. Osteoarthritis (OA) is a common joint disease that causes pain and stiffness. This study explores the role of a protein called vaspin in OA. Researchers collected cartilage samples from humans and mice to study vaspin’s effects. They found that vaspin levels were higher in damaged cartilage, suggesting it may worsen OA. To test this, they used mice genetically modified to produce more or less vaspin. Mice with more vaspin had worse OA symptoms, while those with less had milder symptoms. The team also developed a small antibody called a nanobody to block vaspin. When injected into mice with OA, this nanobody reduced cartilage damage and pain without causing side effects. The study concludes that targeting vaspin could be a promising new approach for treating OA. Future research may focus on developing nanobody treatments for human use. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.