OBJECTIVES: To explore ferroptosis-related genes in osteoporosis through bioinformatic analysis and in vitro study. METHODS: Osteoporosis-related genes were identified from dataset GSE35958 in the Gene Expression Omnibus database; and the ferroptosis-related genes were identified from the FerrDb database. These were intersected with the differentially expressed genes in GSE35958 to obtain ferroptosis-related genes in osteoporosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the differentially expressed genes. And Spearman correlation and protein-protein interaction network analysis were performed. Then, the hub genes of ferroptosis in osteoporosis were screened by Degree, MNC, EPC, MCC and DMNC in Cytoscape software CytoHubba plugin; and analyzed with receiver operating characteristic (ROC) curves. The bone marrow mesenchymal stem cells from osteoporosis patients (osteoporosis group) and non-osteoporosis patients (control group) were subjected to quantitative reverse transcription polymerase chain reaction to detect the messenger RNA expression of ferroptosis hub genes in both groups. RESULTS: A total of 32 differentially expressed genes related to ferroptosis in osteoporosis were identified, including 26 up-regulated genes and 6 down-regulated genes. GO enrichment analysis showed that the identified genes were mainly involved in intercellular adhesion, lipid metabolism and cytokine response. KEGG enrichment analysis showed that the genes were mainly involved in signaling pathways of adhesive plaques, MAPK, PI3K-Akt, and Wnt. Spearman correlation analysis showed correlation among differentially expressed genes. Six hub genes for ferroptosis in osteoporosis were obtained, namely MAPK3, CDKN1A, MAP1LC3A, TNF, RELA, and TGF-β1. ROC curve analysis showed that these hub genes had good diagnostic performance in osteoporosis and may become potential biomarkers of osteoporosis. In vitro experiments confirmed significant differences in these hub genes between the control group and the osteoporosis group (all P<0.05). CONCLUSIONS This study has identified six ferroptosis-related hub genes in osteoporosis, which may be used as novel biomarkers for the early diagnosis and treatment of osteoporosis.
Osteoporosis/genetics* ; Humans ; Computational Biology ; Ferroptosis/genetics* ; Protein Interaction Maps/genetics* ; Gene Ontology ; Mesenchymal Stem Cells/metabolism* ; Gene Expression Profiling ; Databases, Genetic

Liver disease involves a complex interplay of pathological processes, including inflammation, hepatocyte necrosis, and fibrosis. End-stage liver disease (ESLD), such as liver failure and decompensated cirrhosis, has a high mortality rate, and liver transplantation is the only effective treatment. However, to overcome problems such as the shortage of donor livers and complications related to immunosuppression, there is an urgent need for new treatment strategies that need to be developed for patients with ESLD. For instance, hepatocytes derived from donor livers or stem cells can be engrafted and multiplied in the liver, substituting the host hepatocytes and rebuilding the liver parenchyma. Stem cell therapy, especially mesenchymal stem cell therapy, has been widely proved to restore liver function and alleviate liver injury in patients with severe liver disease, which has contributed to the clinical application of cell therapy. In this review, we discussed the types of cells used to treat ESLD and their therapeutic mechanisms. We also summarized the progress of clinical trials around the world and provided a perspective on cell therapy.
Humans ; Cell- and Tissue-Based Therapy/methods* ; End Stage Liver Disease/therapy* ; Hepatocytes ; Mesenchymal Stem Cell Transplantation ; Stem Cell Transplantation