Investigating the improvement of rheumatoid arthritis in rats by deer bone protein through the Keap1/Nrf2-regulated ferroptosis signaling pathway based on transcriptomics

Rheumatoid arthritis (RA) is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present. This can cause joint pain, muscle loss, and other serious problems. Therefore, finding natural anti-RA products and effective treatment strategies is crucial for achieving good prognoses in RA patients. The deer bone is rich in protein, which has the effect of eliminating rheumatism and strengthening muscles and bones. Through multiple gel chromatography purifications, we obtained the deer bone protein (DBP) with a protein content of 76.43%, which was then analyzed using label-free proteomics. Subsequently, an adjuvant arthritis (AA) rat model was established. The ferroptosis pathway was chosen for study based on transcriptomic analysis of AA rat synovial tissue. The molecules with the best docking scores, Nrf2 and Keap1, were then visualized to confirm their validity. Additionally, results from electron microscopy observations, and Western blot (WB) experiments indicated that deer bone protein activates the ferroptosis signaling pathway, alleviating synovial hyperplasia. Therefore, regulating the Keap1/Nrf2 signaling pathway is key to promoting ferroptosis of deer bone protein to improve RA. This study provides new insights into the search for natural foods to improve RA and offers theoretical support for the full development and utilization of Sika deer resources and deer bone products.