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

## TL;DR

This study finds that RIPK3 is linked to cartilage degeneration in osteoarthritis and could be a potential biomarker or treatment target.

## Contribution

The study identifies RIPK3 as spatially associated with cartilage degeneration in OA, linking it to histopathological severity.

## Key findings

- RIPK3 is significantly upregulated in junction and lesioned cartilage tissues of OA patients.
- RIPK3 expression correlates with increased histopathological damage scores in OA cartilage.
- RIPK3 is associated with necroptosis, immune signaling, and extracellular matrix catabolism pathways.

## Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, yet its molecular underpinnings remain incompletely defined. This study aimed to investigate the regional expression pattern of receptor-interacting protein kinase 3 (RIPK3) in OA cartilage and its association with histopathological severity.

Cartilage samples were collected from OA patients and categorized into normal tissue (NT), junction tissue (JT), and lesioned tissue (LT). RNA sequencing was performed to identify differentially expressed genes (DEGs) between NT and JT. Gene enrichment analysis was conducted to explore functional pathways. Immunofluorescence staining was used to validate RIPK3 protein expression and localization.

Transcriptomic analysis identified 140 differentially expressed genes (DEGs) between NT and JT, with several genes, including RIPK3, CCL19, and ITLN1, significantly up-regulated in JT. RIPK3 expression showed a log2 Fold Change of 2.17 (p < 0.01) and displayed higher protein abundance in LT (3.66-fold vs NT), concordant with the transcriptomic trend. This increase correlated with more severe histopathological damage (Mankin score: LT 33.0 vs. NT 5.6; OARSI score: LT 15.8 vs. NT 1.6). Functional enrichment analysis associated RIPK3 with necroptosis, immune signaling and extracellular matrix catabolism. Immunofluorescence staining confirmed spatial accumulation of RIPK3 in LT, consistent with transcriptomic data.

RIPK3 is spatially enriched in degenerative regions of OA cartilage and associates with histopathological damage, suggesting its potential involvement in disease progression. These findings provide new insight into the molecular landscape of OA and support RIPK3 for further evaluation as a biomarker and potential therapeutic target.