Psoralen induces osteoblast differentiation by increasing ESR1 expression in human osteoblasts

Background Osteoporosis, a prevalent metabolic bone disease, is characterized by reduced bone mass and increased risk of fractures. Current therapeutic strategies are limited, warranting the exploration of alternative treatments such as herbal compounds. Psoralen, a natural compound found in traditional Chinese medicine, has been proposed to regulate osteoporosis, but its mechanism of action remains unclear. Methods hFOB1.19 cells were used as an in vitro cell model of osteoporosis. The study used the GeneCards database to search for genes associated with the occurrence and development of osteoporosis. The SwissTargetPrediction online platform, the TM-MC 2.0 database, and the HERB database were used to predict the potential targets of psoralen. The study then analyzed the intersection targets of psoralen and osteoporosis using the Venny 2.1.0 online tool. The intersection targets of psoralen and osteoporosis were imported into the STRING database to obtain the protein-protein interaction network of the intersection targets. Core genes were filtered based on the degree value, and the Cytoscape software was used to visualize the genes. All psoralen targets related to osteoporosis treatment were submitted to the DAVID 6.8 database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The study performed molecular docking of psoralen and target protein. Cell counting kit-8 assay was performed to analyze cell viability. The protein and mRNA expression were analyzed by western blotting assay and quantitative real-time polymerase chain reaction assay, respectively. Alkaline phosphatase (ALP) activity was analyzed through the colorimetric method. ALP content and cell mineralization ability were determined by ALP staining and alizarin red S staining, respectively. Results Through the prediction of psoralen targets related to osteoporosis therapy, the top five genes were identified based on their degree values, which included estrogen receptor 1 (ESR1), tumor necrosis factor (TNF), poly (ADP-ribose) polymerase 1 (PARP1), ataxia telangiectasia-mutated gene (ATM), and epidermal growth factor receptor (EGFR). The GO analysis indicated that these psoralen targets were involved in processes such as DNA repair, signal transduction, regulation of gene expression, DNA binding, and protein binding. The KEGG pathway analysis demonstrated that these genes played a role in the regulation of various signaling pathways, including the TNF signaling pathway, apoptosis, and estrogen signaling pathway. Molecular docking studies revealed that psoralen had a binding affinity for ESR1. Furthermore, the findings showed that psoralen treatment (15 μM) increased ESR1 expression by 4.10-fold in hFOB1.19 cells ( P < 0.05). Treatment with psoralen (15 μM) enhanced ALP activity by 3.70-fold and improved the mineralization capacity of hFOB1.19 cells by 4.42-fold ( P < 0.05). Psoralen treatment also led to an upregulation of RUNX2 by 5.44-fold, β-catenin by 2.54-fold, and cyclinD1 expression by 1.85-fold ( P < 0.05). Moreover, the use of an estrogen antagonist mitigated the effects induced by psoralen in hFOB1.19 cells ( P < 0.05). Conclusion Psoralen promoted osteoblast differentiation by upregulating ESR1 expression in human osteoblasts, suggesting its potential as a therapeutic agent for osteoporosis.