Transcriptomic analysis of expression and function of differential genes in traditional Chinese medicine syndromes of postmenopausal osteoporosis
BACKGROUND: Kidney yin-yang deficiency syndrome in postmenopausal osteoporosis holds particular clinical significance due to its complex features of yin-yang imbalance, and analysis of its differential genes is key to revealing molecular mechanisms. OBJECTIVE: To compare differential gene expression profiles among different kidney deficiency syndromes of postmenopausal osteoporosis, screen for differential genes and signaling pathways associated with kidney yin-yang deficiency syndrome, reveal its molecular biological characteristics, and provide a basis for the objectification of traditional Chinese medicine syndromes. METHODS: Eighteen postmenopausal osteoporosis patients with kidney deficiency syndromes (kidney yang deficiency, kidney yin deficiency, and kidney yin-yang deficiency, 6 cases each) were included, and 6 healthy postmenopausal women served as healthy controls. Transcriptome sequencing was used to screen differential genes, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The expression levels of four target genes (HSP90AB4P, CTU1, ST6GALNAC2, PTGS2) were validated by qRT-PCR. RESULTS AND CONCLUSION: (1) Compared with healthy controls, kidney yin deficiency, and kidney yang deficiency groups, the kidney yin-yang deficiency group had 235, 247, and 4,557 differentially expressed genes, respectively. Intersection analysis of the three comparison groups identified 22 differential genes associated with kidney yin-yang deficiency syndrome (18 up-regulated, 4 down-regulated). (2) qRT-PCR validation showed that the up/down regulation trends of target genes were consistent with transcriptome sequencing results. (3) Gene Ontology analysis showed that biological processes focused on energy metabolism (NAD synthesis and metabolism) and physiological homeostasis (thermogenesis, blood pressure regulation), molecular functions involved immune defense, metabolic regulation, inflammation and signal transduction, ion channel regulation, etc.; cellular components were related to ribosomes, endoplasmic reticulum, nucleus, and tRNA modification. (4) Kyoto Encyclopedia of Genes and Genomes enrichment identified 60 pathways, including apoptotic cell clearance, nuclear factor kappa B, tumor necrosis factor, interleukin-17, vascular endothelial growth factor, forkhead box O signaling pathways, and metabolic pathways. (5) These findings suggest that postmenopausal osteoporosis with kidney yin-yang deficiency syndrome is a comprehensive manifestation of multidimensional molecular network imbalance, related to ribosomal synthesis disorders, non-coding RNA and signal transduction and transcriptional regulation, immune-inflammatory regulation, and metabolic transport.