Comprehensive analysis of circRNA expression profiles in postmenopausal women differing in bone mineral density.

Postmenopausal osteoporosis (PMOP) seriously endangers the bone health of older women. Although there are currently indicators to diagnose PMOP, early diagnostic biomarkers are lacking. Circular ribonucleic acid (circRNA) has a stable structure, regulates gene expression, participates in the pathological process of disease, and has the potential to become a biomarker. The purpose of this study was to investigate circRNAs that could be used to predict patients with early PMOP. Ribonucleic acid (RNA) sequencing was performed on peripheral blood leukocytes from 15 female patients to identify differential circRNAs between different groups. Using bioinformatics analysis, enrichment analysis was performed to discover relevant functions and pathways. CircRNA-micro ribonucleic acid (miRNA) interaction analysis and messenger ribonucleic acid (mRNA) prediction and network construction help us to understand the relationship between circRNA, miRNA, and mRNA. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the gene expression of candidate circRNAs. We screened out 2 co-expressed differential circRNAs, namely hsa_circ_0060849 and hsa_circ_0001394. By analyzing the regulatory network, a total of 54 miRNAs and 57 osteoporosis-related mRNAs were identified, which, as potential downstream target genes of hsa_circ_0060849 and hsa_circ_0001394, may play a key role in the occurrence and development of PMOP. The occurrence and development of PMOP is regulated by circRNAs, and hsa_circ_0060849 and hsa_circ_0001394 can be used as new diagnostic markers and therapeutic targets for early PMOP.

Identification of Drug Targets and Agents Associated with Ferroptosis-related Osteoporosis through Integrated Network Pharmacology and Molecular Docking Technology.

BACKGROUND: Osteoporosis is a systemic bone disease characterized by progressive reduction of bone mineral density and degradation of trabecular bone microstructure. Iron metabolism plays an important role in bone; its imbalance leads to abnormal lipid oxidation in cells, hence ferroptosis. In osteoporosis, however, the exact mechanism of ferroptosis has not been fully elucidated. OBJECTIVE: The main objective of this project was to identify potential drug target proteins and agents for the treatment of ferroptosis-related osteoporosis. METHODS: In the current study, we investigated the differences in gene expression of bone marrow mesenchymal stem cells between osteoporosis patients and normal individuals using bioinformatics methods to obtain ferroptosis-related genes. We could predict their protein structure based on the artificial intelligence database of AlphaFold, and their target drugs and binding sites with the network pharmacology and molecular docking technology. RESULTS: We identified five genes that were highly associated with osteoporosis, such as TP53, EGFR, TGFB1, SOX2 and MAPK14, which, we believe, can be taken as the potential markers and targets for the diagnosis and treatment of osteoporosis. Furthermore, we observed that these five genes were highly targeted by resveratrol to exert a therapeutic effect on ferroptosis-related osteoporosis. CONCLUSION: We examined the relationship between ferroptosis and osteoporosis based on bioinformatics and network pharmacology, presenting a promising direction to the pursuit of the exact molecular mechanism of osteoporosis so that a new target can be discovered for the treatment of osteoporosis.

Mesenchymal stem/stromal cells-derived exosomes for osteoporosis treatment.

Osteoporosis is a systemic bone disease, which leads to decreased bone mass and an increased risk of fragility fractures. Currently, there are many anti-resorption drugs and osteosynthesis drugs, which are effective in the treatment of osteoporosis, but their usage is limited due to their contraindications and side effects. In regenerative medicine, the unique repair ability of mesenchymal stem cells (MSCs) has been favored by researchers. The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms, which may have therapeutic effects. In this review, we describe the regulatory effects of MSCs-derived exosomes on osteoclasts, osteoblasts, and bone immunity. We aim to summarize the preclinical studies of exosome therapy in osteoporosis. Furthermore, we speculate that exosome therapy can be a future direction to improve bone health.

Comprehensive analysis of lncRNA expression profiles in postmenopausal osteoporosis.

To explore the key lncRNAs affecting postmenopausal osteoporosis (PMOP) progression, the transcriptome sequencing of peripheral blood mononuclear cells from fifteen early postmenopausal women, according to bone mineral density, were divided into groups of osteoporosis, osteopenia and normality, in each of which the expression profiles of lncRNAs was investigated. From the results we observed nine candidates of lncRNAs, which were to be compared with miRBase, and found that MIR22HG as one candidate of lncRNA was most likely to be directly used as miRNA precursor. Based on the KEGG annotation and lncRNA-miRNA-mRNA-KEGG network, we analyzed the potential role of candidate lncRNAs. The results showed that the expression profiles of lncRNAs could help identify the novel ones involved in the progression of PMOP, and that MIR22HG could serve as a miRNA precursor to regulate FoxO signaling pathway in bone metabolism. Our findings can be of great help in predicting and diagnosing early PMOP.