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Exp. Mol. Med., Mar 03 2025, | https://doi.org/10.1038/s12276-025-01418-z
Blockade of the vaspin-AP-1 axis inhibits arthritis development
Jimin Jeon 1,8, Chanmi Cho 1,2,8, Seoyeong Kim 1, Hyeran Kim 3, Hyemi Lee 1, Seok Jung Kim 4, Hwangseo Park 5, Ji Hoon Yu 6, Sangho Lee 1, Kyu-Sun Lee 3,*, Juyeon Jung 3,7,* and Siyoung Yang 1,*
1Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
2Center for Systems Biology, Massachusetts General Hospital Research Institute; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
4Department of Orthopedic Surgery, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Republic of Korea.
5Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
6New Drug Development Center, DaeguGyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea.
7School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
8These authors contributed equally: Jimin Jeon, Chanmi Cho.
2Center for Systems Biology, Massachusetts General Hospital Research Institute; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
4Department of Orthopedic Surgery, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Republic of Korea.
5Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
6New Drug Development Center, DaeguGyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea.
7School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
8These authors contributed equally: Jimin Jeon, Chanmi Cho.
*Corresponding authors: correspondence to Kyu-Sun Lee, Juyeon Jung or Siyoung Yang
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.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-05)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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