Chinese giant salamander ( <em>Andrias davidianus</em> ) bone collagen peptides attenuate osteoarthritis symptoms through <em>lincRNA-Cox2</em> /NF-&amp;kappa;B pathway

Osteoarthritis (OA) is a commonly occurring regressive articulation disease. Bioactive peptides derived from food have been reported to have excellent inhibitory effects on inflammatory responses. In this study, we evaluated the effects of Chinese giant salamander bone collagen peptides (CBCPs) on macrophage inflammation stimulated by lipopolysaccharide (LPS), and explored its protective effect against OA by an animal model of rat osteoarthritis. CBCPs were prepared from Chinese giant salamander bone by enzymatic hydrolysis. Under the optimal digestion conditions of neutral protease 7000 U/g, temperature 47 ℃, pH 7.0, material-liquid ratio 1:10, and digestion 6 h, CBCPs showed the strongest anti-inflammatory activity. After ultrafiltration, the 300-1000 Da peptide (named <em>Ad-</em>CP) showed the strongest anti-inflammatory effect, significantly reducing the release of NO, and the serection of IL-6, and TNF-α in inflammatory macrophages and inhibiting the chemotactic effect of macrophages. RNA FISH experiments revealed that <em>lincRNA-Cox2 </em>expression induced by LPS was inhibited by <em>Ad</em>-CP. Mechanistic analysis showed that <em>Ad</em>-CP suppressed NF-κB signaling via <em>lincRNA</em>-<em>Cox2 </em>by small interfering RNA, thereby reducing LPS-induced macrophage inflammation. Analysis of a rat osteoarthritis model showed that treatment with <em>Ad</em>-CP inhibited joint damage, macrophage infiltration and cartilage damage, and down-regulated the levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the joint fluid of OA rats. And treatment of <em>Ad</em>-CP suppressed <em>lincRNA-Cox2</em> expression and inhibited the phosphorylation of NF-κB p65 and IκBα in knee joint tissue. In conclusion, <em>Ad</em>-CP alleviated the symptoms of osteoarthritis in OA rats through targeting the <em>lincRNA</em>-<em>Cox2</em>/NF-κB axis.