Abstract: BACKGROUND: Kidney yin-yang deficiency syndrome in postmenopausal osteoporosis holds particular clinical significance due to its complex characteristics. Analysis of its differential genes is crucial for uncovering its molecular mechanisms.
OBJECTIVE: To identify differential genes and signaling pathways associated with kidney yin-yang deficiency syndrome by comparing differential gene expression profiles across different kidney deficiency syndromes in postmenopausal osteoporosis, thereby revealing its molecular biological characteristics and providing an objective basis for traditional Chinese medicine syndrome differentiation.
METHODS: Eighteen postmenopausal osteoporosis patients with kidney deficiency syndromes (six cases each of kidney yang deficiency, kidney yin deficiency, and kidney yin-yang deficiency) were enrolled, and an additional six healthy postmenopausal women were included as a healthy control group. Transcriptome sequencing was used to screen for 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, and PTGS2) were validated by qRT-PCR.
RESULTS AND CONCLUSION: (1) Compared with the healthy control group, the kidney yin-yang deficiency syndrome group, the kidney yin deficiency group, and the kidney yang deficiency group yielded 235, 247, and 4 557 differentially expressed genes, respectively. Intersection analysis of the three comparison groups identified 22 differential genes associated with the kidney yin-yang deficiency syndrome group (18 up-regulated and 4 down-regulated). (2) qRT-PCR showed that the up-regulation and down-regulation trends of the target genes were consistent with the transcriptome sequencing results. (3) Gene Ontology analysis showed that biological processes focused on energy metabolism (nicotinamide adenine dinucleotide synthesis and metabolism) and physiological homeostasis (thermogenesis and blood pressure regulation); molecular functions involved immune defense, metabolic regulation, inflammation and signal transduction, and ion channel regulation; and cellular components were associated with ribosomes, endoplasmic reticulum, nucleus, and transfer RNA modification. (4) Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 60 pathways, including apoptotic cell clearance, nuclear factor κB, tumor necrosis factor, interleukin 17, vascular endothelial growth factor, forkhead box O signaling pathways, and metabolic pathways. Overall, these findings suggest that postmenopausal osteoporosis with kidney yin-yang deficiency syndrome is a comprehensive manifestation of multidimensional molecular network imbalance, associated with ribosomal synthesis disorders, non-coding RNA-mediated signal or transcriptional regulation, immune-inflammatory regulation, and metabolic transport.

Key words: postmenopausal osteoporosis, kidney yin-yang deficiency syndrome, differential genes, transcriptome sequencing, signaling pathway