Investigating the role of SMOX in rheumatoid arthritis

  • Mol Immunol. 2026 Jan:189:235-246. doi: 10.1016/j.molimm.2025.11.018.
Zuning Jiang  1 Ruojia Zhang  1 Ya Han  1 Ruiyao Sun  1 Mingze Kong  1 Yuang Zhang  1 Junling Li  1 Guanhua Song  2 Li Qiao  3 Lin Wang  4
Affiliations
  • 1. Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences; NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences; Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong, China.
  • 2. Department of Immunology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 3. Department of Orthopaedic Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Shandong, China. Electronic address: [email protected].
  • 4. Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences; NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences; Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong, China. Electronic address: [email protected].
Abstract

Rheumatoid arthritis (RA) is pathologically marked by joint inflammation and damage. Although the association between spermidine and RA has been recognized, the precise contribution of spermine oxidase (SMOX)-the enzyme catalyzing spermidine synthesis-to RA pathogenesis remains undefined. It's observed in this study that SMOX was responsible for inflammatory stimuli that its expression increased obviously when RA-associated fibroblast-like synoviocytes (FLSs) were challenged by inflammatory factors. Functionally, silencing SMOX could inhibit migration, invasion, and cytokine production, but induced Apoptosis of RA-FLS. Moreover, inhibition of SMOX using JNJ-9350 yielded anti-inflammatory effects comparable to those achieved by gene silencing in RA-FLS. In vivo experiments demonstrated that JNJ-9350 could effectively reduce the severity of arthritis, minimize histopathological damage, and prevent bone erosion in Collagen antibody-induced arthritis (CAIA) mice. The present results indicate that SMOX is implicated in the development of RA and suggest that targeting SMOX could be a novel treatment strategy.

Keywords
Fibroblast-like synoviocyte; Rheumatoid Arthritis; Spermidine; Spermine Oxidase.
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