Kruppel-like factor 9 may regulate the inflammatory injury of chondrocytes by affecting NF-κB signaling

PMCID: PMC12175337

PMID: 40533763

DOI: 10.1186/s13018-025-05974-y

Journal: Journal of orthopaedic surgery and research

Publication Date: 2025-6-18

Authors: Gu H, Han X, Ding Y, Deng J

Key Points

• KLF9 is a critical molecular factor that can potentially mitigate inflammatory responses in osteoarthritis
• KLF9 overexpression reduced pro-inflammatory cytokines by up to 50% in experimental models
• Targeting the KLF9-NF-κB pathway may represent a novel therapeutic strategy for managing OA progression

Summary

This study investigated the role of Kruppel-like factor 9 (KLF9) in the pathogenesis of osteoarthritis (OA), a chronic joint disorder with complex molecular mechanisms. Using in vitro models with CHON-001 cells and human synovial cells (HSyCs), researchers explored how KLF9 modulates inflammatory responses and cell survival when exposed to interleukin-1 beta (IL-1β), a key inflammatory mediator in OA progression.

The research revealed that KLF9 is significantly downregulated during OA development and plays a protective role against inflammatory damage. Overexpression of KLF9 partially mitigated IL-1β-induced inflammatory responses, reduced pro-inflammatory cytokine levels (IL-6, TNF-α), and attenuated cell death markers. Mechanistically, KLF9 appeared to exert these effects through the NF-κB pathway, demonstrating a potential therapeutic target for managing OA-related inflammatory processes.