(5R)-5-hydroxytriptolide (LLDT-8) prevents collagen‑induced arthritis through OPG/RANK/RANKL signaling in a rat model of rheumatoid arthritis

Abstract

(5R)‑5‑hydroxytriptolide (LLDT‑8) extracts from Tripterygium have anti‑inflammatory, antineoplastic and immunity adjustment functions. The present study used a collagen‑induced arthritis (CIA) model to evaluate whether LLDT‑8 prevents collagen‑induced arthritis, and investigated the signaling underlying this. Male Sprague‑Dawley rats were induced to generate CIA, mimicking rheumatoid arthritis (RA). The presence of arthritis was determined using RA progression scores. The inflammatory cytokines interleukin (IL)‑1β, IL‑6 and nuclear factor‑κB were detected using enzyme‑linked immunosorbent assay kits. Induced nitric oxide synthase (iNOS) and matrix metalloprotease (MMP)‑13 protein expression were measured using western blot analysis. Lastly, reverse transcription‑quantitative polymerase chain reaction was used to evaluate osteoprotegerin (OPG) and receptor activator of nuclear factorκB (RANK) gene expression. LLDT‑8 improved RA progression scores and reduced the incidence and severity of CIA. Furthermore, LLDT‑8 administration inhibited collagen‑induced inflammation and iNOS protein expression in arthritic rats. The current data indicated that MMP‑13 production was suppressed and OPG/RANKL expression was increased by LLDT‑8 treatment in the arthritic rat. The present results suggest that LLDT‑8 attenuates CIA through OPG/RANK/RANK ligand signaling in a rat model of RA.