Background: Dysregulated macrophage activation is a cornerstone of rheumatoid arthritis (RA) pathogenesis. We previously identified LncRNA ANKRD33B-2 as a novel regulator of macrophage pyroptosis in vitro. However, its functional role in RA pathophysiology in vivo and its therapeutic potential remain unexplored.

Objectives: To investigate the in vivo role of Lnc-ANKRD33B-2 in the synovial inflammation and joint destruction of RA, and to evaluate the efficacy of its targeted inhibition as a potential therapeutic strategy.

Methods: A collagen-induced arthritis (CIA) model was established in rats. An adenovirus vector delivering shRNA against Lnc-ANKRD33B-2 (2.5×10 ¹⁰ viral genomes per rat) was administered via intra-articular injection to achieve local knockdown. Therapeutic effects were assessed by: arthritis clinical scoring; histological evaluation (H&E staining) of synovial hyperplasia, inflammatory infiltration, and pannus formation; and quantification of pro-inflammatory cytokine mRNA levels in joint tissues via qPCR.

Results: Compared to the CIA model group (clinical score: 7.67 ± 1.25), targeted knockdown of Lnc-ANKRD33B-2 for four weeks significantly ameliorated disease severity, reducing the joint swelling index by approximately 50% (P < 0.001). Histopathological analysis demonstrated markedly attenuated synovial hyperplasia, minimal inflammatory cell infiltration, and suppressed pannus formation. Concordantly, the mRNA expression of IL-1β, IL-6, TNF-α, and IFN-γ in joint tissues was significantly downregulated (P < 0.05).

Conclusions: This study provides the first in vivo evidence that Lnc-ANKRD33B-2 is a key driver of synovitis and joint destruction in RA. Targeted inhibition of this lncRNA represents a promising novel therapeutic strategy for RA by effectively alleviating clinical symptoms and suppressing local inflammatory responses.

Figure 1.

Pathological changes in the joints of CIA model rats.

Figure 2.

Effect of Lnc-ANKRD33B-2-interfering adenovirus on the histopathological changes of synovial and cartilage tissues in rat joints.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.