VEGFA, MYC, and JUN are abnormally elevated in the synovial tissue of patients with advanced osteoarthritis

Sci Rep. 2025 Jan 15;15(1):2066. doi: 10.1038/s41598-024-80551-7.

Abstract

Osteoarthritis (OA), affecting > 500 million people worldwide, profoundly affects the quality of life and ability to work. The mitogen-activated protein kinase (MAPK) signaling pathway plays an essential role in OA. To address the lack of studies focused on synovial cells in OA, we evaluated the expression patterns and roles of the MAPK signaling pathway components in OA synovial tissues using bioinformatics. The JUN, MYC, and VEGFA expression levels were significantly higher in the synovial tissues of patients with OA than in control tissues. These loci were closely related to abnormal proliferation, inflammation, and angiogenesis in the synovial tissues of patients with OA. We speculate that Myc and VEGFA activate the p38-MAPK signaling pathway to further activate Jun, thereby promoting abnormal inflammation, proliferation, and angiogenesis in OA synovial tissue. The high MYC, JUN, and VEGFA expression was positively correlated with the patients' K-L score, pain time, and synovial score. Furthermore, the high p38-MAPK and P-p38-MAPK expression confirmed that the abnormal expression and activation of the MAPK signaling pathway occurred in the synovial tissue of patients with OA. Our findings may provide a new direction for the clinical diagnosis and treatment of OA and insights into its pathogenesis.

Keywords: JUN; MAPK; MYC; Osteoarthritis; Synovial tissue; VEGFA.

MeSH terms

  • Aged
  • Female
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / pathology
  • Proto-Oncogene Proteins c-jun / metabolism
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins c-myc* / metabolism
  • Synovial Membrane* / metabolism
  • Synovial Membrane* / pathology
  • Vascular Endothelial Growth Factor A* / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • VEGFA protein, human
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins c-jun
  • MYC protein, human
  • p38 Mitogen-Activated Protein Kinases