Abstract
BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease accompanied with joint destruction that often leads to disability. Wang-Bi capsule (WB), a traditional Chinese medicine-based herbs formula, has exhibited inhibition effect on joint destruction of collagen-induced arthritis (CIA) animal model in our previous study. But its molecular mechanisms are still obscure.MethodsCIA rats were treated intragastrical with WB for eight weeks, and the effect of joints protection were evaluated by hematoxylin and eosin (H&E) staining, safranin O fast green staining, tartrate-resistant acid phosphatase (TRAP) staining and micro‑CT scanning analysis. The transcriptomic of tarsal joints were used to investigate how WB alleviated joint destruction.ResultsThe histological examination of ankle joints showed WB alleviated both cartilage damage and bone destruction of CIA rats. This protective effect on joints were further evidenced by micro-CT analysis. The transcriptomic analysis showed that WB prominently changed 12 KEGG signaling pathways (“calcium signaling pathway”, “cAMP signaling pathway”, “cell adhesion molecules”, “chemokine signaling pathway”, “complement and coagulation cascades”, “MAPK signaling pathway”, “NF-kappa B signaling pathway”, “osteoclast differentiation”, “PI3K-Akt signaling pathway”, “focal adhesion”, “Gap junction” and “Rap1 signaling pathway”) associated with bone or cartilage. Several genes (including Il6, Tnfsf11, Ffar2, Plg, Tnfrsf11b, Fgf4, Fpr1, Siglec1, Vegfd, Cldn1, Cxcl13, Chad, Arrb2, Fgf9, Egfr) regulating bone resorption, bone formation and cartilage development were identified by further analysis. Meanwhile, these differentially expressed genes were validated by real-time quantitative PCR.ConclusionsOverall, the protective effect of WB treatment on joint were confirmed in CIA rats, and its basic molecular mechanisms may be associated with regulating some genes (including Il6, Tnfsf11, Ffar2 and Plg etc.) involved in bone resorption, bone formation and cartilage development.
Highlights
Rheumatoid arthritis (RA) is a chronic, autoimmune disease that is accompanied by persistent inflammation of synovial tissue as well as joint destruction
By KEGG analysis of differentially expressed genes (DEGs) in Mod-VS-Nor and Wang-Bi capsule (WB)-VS-Mod, we found 12 obviously enriched (P value < 0.05) signaling pathways associated with bone or cartilage, including “calcium signaling pathway”, “cell adhesion molecules (CAMs)”, “complement and coagulation cascades”, “osteoclast differentiation”, “PI3K-Akt signaling pathway”, “cAMP signaling pathway”, “chemokine signaling pathway”, “NF-kappa B signaling pathway”, “MAPK signaling pathway”, “focal adhesion”, “Rap1 signaling pathway” and “gap junction” (Fig. 4b)
WB regulated the levels of some genes that controlled bone and cartilage function in rats with collagen-induced arthritis (CIA) Having identified the 12 signaling pathways that regulated bone and cartilage function, we focused on the DEGs belonging to these signaling pathways
Summary
Rheumatoid arthritis (RA) is a chronic, autoimmune disease that is accompanied by persistent inflammation of synovial tissue as well as joint destruction. Joint destruction often interferes with physical function and even results in disability, which further affects productivity. Many earlier studies indicated that joint destruction was correlated with signs and symptoms of inflammation, and some patients with RA have benefited from anti-inflammatory therapies. Joint destruction still occurs with a high incidence after anti-inflammatory treatment. Anti-inflammatory drugs are not sufficient to protect joints, and agents that can directly inhibit joint destruction are essential for RA patients. Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied with joint destruction that often leads to disability. Wang-Bi capsule (WB), a traditional Chinese medicine-based herbs formula, has exhibited inhibition effect on joint destruction of collagen-induced arthritis (CIA) animal model in our previous study.
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