Knockdown of UBD Ameliorates Experimental Rheumatoid Arthritis by Suppressing TLR4/Myd88/NF-κB and P38/MAPK Pathway.

Abstract

Background/aims: Ubiquitin D (UBD), a member of the ubiquitin-like modifier (UBL) family, is significantly overexpressed in various cancers and is positively correlated with tumor progression. However, the role and underlying mechanisms of UBD in rheumatoid arthritis (RA) remain poorly understood. This study aimed to investigate the effects of UBD knockdown on the progression of RA.

Materials: We employed the type II collagen and incomplete Freund's adjuvant (CIA) rat model. A variety of analytical techniques were employed, including hematoxylin and eosin (H&E) staining, Safranin O and Fast Green staining, tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis, to elucidate the mechanisms involved.

Results: UBD knockdown correlated with diminished cartilage and bone erosion, reduced counts of TRAP-positive osteoclasts, and enhanced Safranin O staining of the cartilage. Additionally, the knockdown significantly reduced serum levels of PGE2, TNF-α, TIMP-1, IL-1β, MMP-9, and IL-6 in CIA rats. Furthermore, UBD knockdown markedly suppressed the expression levels of phosphorylated p38, TLR4, MyD88, and phosphorylated p65, suggesting a critical role in modulating inflammatory signaling pathways in RA.

Conclusion: Collectively, these results suggested that knockdown of UBD significantly alleviated arthritis progression in the CIA rat model, highlighting UBD as a potential therapeutic target and a promising prognostic biomarker for RA.