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RIPK3 is spatially associated with cartilage degeneration in osteoarthritis: integrative transcriptomic and

Lei Wang1, Jing Tang2,3, Lei Niu2,4

  • 1Department of Trauma and Joint Surgery, The Fifth People's Hospital of Ningxia Hui Autonomous Region, Shizuishan, 753000, Ningxia, China.

Journal of Orthopaedic Surgery and Research
|November 11, 2025
PubMed
Abstract

Insights

Receptor-interacting protein kinase 3 (RIPK3) is found in damaged osteoarthritis cartilage and correlates with disease severity. This suggests RIPK3 may be a biomarker and therapeutic target for osteoarthritis progression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with poorly understood molecular causes.
  • Cartilage degradation is a hallmark of OA, necessitating research into its underlying molecular mechanisms.

Purpose of the Study:

  • To investigate the regional expression of receptor-interacting protein kinase 3 (RIPK3) in OA cartilage.
  • To determine the association between RIPK3 expression and the histopathological severity of OA.

Main Methods:

  • RNA sequencing to identify differentially expressed genes (DEGs) in OA cartilage.
  • Immunofluorescence staining to validate RIPK3 protein expression and localization.
  • Correlation analysis between RIPK3 levels and OA histopathological scores (Mankin, OARSI).

Main Results:

  • RIPK3 was significantly upregulated in lesioned OA cartilage compared to normal tissue (log2 Fold Change 2.17).
  • RIPK3 protein abundance increased with disease severity, correlating with higher Mankin and OARSI scores.
  • Functional enrichment analysis linked RIPK3 to necroptosis, immune signaling, and extracellular matrix degradation.

Conclusions:

  • RIPK3 is spatially enriched in degenerative OA cartilage regions.
  • RIPK3 expression correlates with OA histopathological damage, indicating its role in disease progression.
  • RIPK3 presents potential as a biomarker and therapeutic target for osteoarthritis.
Keywords:
Cartilage degenerationMulti-regional transcriptomicsOsteoarthritisRIPK3

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