Transcriptome Sequencing Reveals Multi-Target Regulatory Networks of the Renin-Angiotensin System in Postmenopausal...

Postmenopausal Osteoporosis (PMOP) is a common disease characterized by reduced bone mass and destruction of the bone microstructure, which severely affects the quality of life of postmenopausal women. This study aims to reveal the molecular mechanism of PMOP through transcriptome sequencing technology, with a focus on the multi-target regulatory network of the Renin-Angiotensin System (RAS) pathway, and to explore potential Traditional Chinese Medicine (TCM) intervention strategies.

In this study, a PMOP rat model was established by bilateral ovariectomy. High-throughput sequencing technology was used to analyze the differences in gene expression between the model group and the sham operation group. Bioinformatics methods were employed to screen key genes and signaling pathways. The expression of key genes was verified through qRT-PCR, and potential TCM intervention targets were predicted based on the CoreMine database.

The study identified 144 differentially expressed genes in the PMOP model group, with 132 upregulated and 12 downregulated. GO and KEGG analyses revealed significant enrichment in extracellular matrix organization, the PI3K-Akt signaling pathway, etc. GSVA analysis further indicated that the RAS pathway was significantly activated in PMOP, and immune infiltration analysis revealed abnormal changes in immune cells such as B cells and mast cells. qRT-PCR verified the high expression of RAS-related genes, such as ACE and REN. Through the prediction of TCM, 43 potentially effective TCMs were identified, such as Epimedii Folium and Chuanxiong Rhizoma. Their effects are consistent with TCM theories such as tonifying the kidney and promoting blood circulation to remove blood stasis.

The research findings suggest that the abnormal activation of the RAS pathway may be involved in the pathogenesis of PMOP through mechanisms such as regulating vasoconstriction and inflammatory responses. The alteration of the immune microenvironment further exacerbates the imbalance of bone metabolism. The predicted TCM may regulate bone metabolism through multi-target interventions, thus providing a new research direction for the treatment of PMOP.

This study systematically reveals the key role of the RAS pathway in PMOP and proposes potential TCM intervention strategies, providing an important basis for mechanistic research on PMOP and the integration of traditional Chinese and Western medicine treatments. In the future, it is necessary to further verify the specific mechanisms of action and clinical efficacy of TCM.