Mechanistic insights into how Cervi Cornus Colla regulates the intestinal flora-bile acid metabolic pathway to alleviate steroid-induced osteonecrosis of the femoral head in a rat model

Chai Jinlian; Liang Xuezhen; Sun Tiefeng; Li Shudong; Li Wei; Li Guangzheng; Yu Huayun; Wang Ping

doi:10.12307/2026.744

Abstract：BACKGROUND:Cervi Cornus Colla,which contains bioactive proteoglycans and other bone-targeting components,demonstrates therapeutic potential by modulating gut microbiota composition and bile acid metabolism.Through the gut-bone axis signaling pathway,Cervi Cornus Colla effectively ameliorates bone metabolic disorders associated with steroid-induced osteonecrosis of the femoral head. OBJECTIVE:To investigate the intervention effect of Cervi Cornus Colla on steroid-induced osteonecrosis of the femoral head in rat models and its potential protective mechanism through the"gut-bone axis." METHODS:Thirty Sprague-Dawley rats were randomly divided into three groups:control,model and Cervi Cornus Colla treatment groups.To establish a steroid-induced osteonecrosis of the femoral head model,rats in the model and Cervi Cornus Colla groups received intramuscular gluteal injections of methylprednisolone sodium succinate during the first 3 days of each week for 3 consecutive weeks.Concurrently,the rats in the Cervi Cornus Colla group were administered Cervi Cornus Colla via oral gavage,and those in the control group and the model group received equal volume of purified water via oral gavage for 6 consecutive weeks.Pathological changes in the femoral head were evaluated using hematoxylin-eosin and Masson staining.The serum interleukin-1β level was detected by ELISA.Western blot analysis assessed the expression of Runt-related transcription factor 2 and type Ⅰ collagen a1 protein in the femoral head.Gut microbiota diversity was analyzed via 16SrDNA sequencing,and integrated with prior fecal metabolomics data to explore potential mechanistic correlations. RESULTS AND CONCLUSION:(1)Compared with the model group,Cervi Cornus Colla significantly reduced empty lacunae rate and adipocyte infiltration,increased collagen fiber content and improved trabecular bone structure(P<0.05).Additionally,Cervi Cornus Colla markedly downregulated serum interleukin-1β levels and upregulated Runt-related transcription factor 2 and type Ⅰ collagen a1 protein expressions(P<0.05).(2)Gut microbiota analysis revealed that compared with the model group,Cervi Cornus Colla intervention significantly reduced the relative abundance of Firmicutes at the phylum level and markedly altered the abundances of Candidatus_Saccharimonas,Turicibacter,Fusobacterium,and UCG_007 at the genus level.(3)Spearman correlation analysis showed that Candidatus_Saccharimonas was positively correlated with β-muricholic acid,cholic acid,and bile acids,while Turicibacter,Fusobacterium,and UCG_007 were negatively correlated with β-muricholic acid,cholic acid,and taurine.(4)Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis further revealed significant enrichment in secondary bile acid biosynthesis,primary bile acid biosynthesis,and taurine metabolism pathways(P<0.05).To conclude,Cervi Cornus Colla may alleviate glucocorticoid-induced femoral head injury by regulating gut microbiota and its related metabolites,thereby influencing bile acid and taurine metabolic pathways.