中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (25): 6446-6454.doi: 10.12307/2026.479

• 骨组织构建 bone tissue construction • 上一篇    下一篇

转录组学分析绝经后骨质疏松症中医证候差异基因表达及功能

何艳艳1，2，葛继荣1，2，李生强1，2，陈  玄1，2，黄景文1，2，黄小彬1，2，薛立鹏1，2   

  1. 1福建省中医药科学院骨质疏松证候基因组学重点研究室，福建省福州市  350003；2福建省中西医结合防治骨质疏松重点实验室(福建省中医药科学院，福建中医药大学附属康复医院)，福建省福州市   350003
  • 收稿日期:2025-10-29 修回日期:2026-03-10 出版日期:2026-09-08 发布日期:2026-04-17
  • 通讯作者: 葛继荣，博士，副院长，福建省中医药科学院骨质疏松证候基因组学重点研究室，福建省福州市 350003；福建省中西医结合防治骨质疏松重点实验室(福建省中医药科学院，福建中医药大学附属康复医院)，福建省福州市 350003
  • 作者简介:何艳艳，女，1994年生，福建省莆田市人，汉族，2021年福建省中医药大学毕业，硕士，助理实验师，医师，主要从事中西医结合防治骨质疏松症方面的研究。
  • 基金资助:
    福建省科技厅省属公益类科研院所基本科研专项(2023R1003002)，项目负责人：何艳艳；福建省科技厅省自然科学基金项目(2025J01922)，项目负责人：何艳艳；福建省科技厅省属公益类科研院所基本科研专项(2023R1003001)，项目负责人：薛立鹏；福建省科技厅省自然科学基金项目(2023J01854)，项目负责人：黄小彬；福建中医药大学中医骨伤科学学科开放课题(XGS2023016)，项目负责人：黄小彬

Transcriptomic analysis of expression and function of differential genes in traditional Chinese medicine syndromes of postmenopausal osteoporosis

He Yanyan1, 2, Ge Jirong1, 2, Li Shengqiang1, 2, Chen Xuan1, 2, Huang Jingwen1, 2, Huang Xiaobin1, 2, Xue Lipeng1, 2   

  1. 1Key Research Laboratory of Osteoporosis Symptom Genomics, Fujian Academy of Chinese Medical Sciences, Fuzhou 350003, Fujian Province, China; 2Fujian Key Laboratory of Integrative Medicine for Osteoporosis Prevention and Control (Fujian Academy of Chinese Medical Sciences, Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine), Fuzhou 350003, Fujian Province, China
  • Received:2025-10-29 Revised:2026-03-10 Online:2026-09-08 Published:2026-04-17
  • Contact: Ge Jirong, PhD, Key Research Laboratory of Osteoporosis Symptom Genomics, Fujian Academy of Chinese Medical Sciences, Fuzhou 350003, Fujian Province, China; Fujian Key Laboratory of Integrative Medicine for Osteoporosis Prevention and Control (Fujian Academy of Chinese Medical Sciences, Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine), Fuzhou 350003, Fujian Province, China
  • About author:He Yanyan, MS, Assistant experimentalist, Physician, Key Research Laboratory of Osteoporosis Symptom Genomics, Fujian Academy of Chinese Medical Sciences, Fuzhou 350003, Fujian Province, China; Fujian Key Laboratory of Integrative Medicine for Osteoporosis Prevention and Control (Fujian Academy of Chinese Medical Sciences, Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine), Fuzhou 350003, Fujian Province, China
  • Supported by:
    Basic Scientific Research Special Project of Fujian Provincial Department of Science and Technology for Provincial Public Welfare Research Institutes, No. 2023R1003002 (to HYY); Natural Science Foundation Project of Fujian Provincial Department of Science and Technology, No. 2025J01922 (to HYY); Basic Scientific Research Special Project of Fujian Provincial Department of Science and Technology for Provincial Public Welfare Research Institutes, No. 2023R1003001 (to XLP); Natural Science Foundation Project of Fujian Provincial Department of Science and Technology, No. 2023J01854 (to HXB); Open Project of the Orthopedics and Traumatology of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, No. XGS2023016 (to HXB) 

PDF

2

摘要：



文题释义：
绝经后骨质疏松：是一种与女性绝经密切相关的、以骨量减少、骨微结构破坏、骨脆性增加和易发生骨折为特征的全身性代谢性骨病。它是原发性骨质疏松中最常见的一种类型，骨折是其主要并发症和最严重后果，常见部位为脊柱、髋部和腕部，严重影响患者的生活质量甚至可能导致死亡。
转录组学：研究生物特定细胞/组织特定状态下的所有转录本(含mRNA、长链非编码RNA、微小RNA等)，核心是解析基因表达动态与调控规律。常用转录组测序技术检测不同生理/病理状态下转录本种类、丰度差异，筛选差异基因，进而构建调控通路、揭示分子机制。医学上可用于疾病标志物筛选、药物靶点发现，如在此次研究中，助力识别证型相关差异基因，为解析疾病机制提供分子依据。

背景：绝经后骨质疏松症肾阴阳两虚证因其兼具阴阳失衡的复杂特征，在临床诊疗中具有特殊意义，而对其差异基因的分析是揭示分子机制的关键。
目的：通过比较绝经后骨质疏松症不同肾虚证候的差异基因表达谱，筛选肾阴阳两虚证关联差异基因及信号通路，揭示其分子生物学特征，为中医证候客观化提供依据。
方法：纳入18 例绝经后骨质疏松症肾虚证患者(肾阳虚、肾阴虚、肾阴阳两虚证各6例)，另外选择6 例健康绝经后女性作为健康对照组。运用转录组测序筛选差异基因，进行基因本体论与京都基因与基因组百科全书富集分析，并通过qRT-PCR对4个目标基因(HSP90AB4P、CTU1、ST6GALNAC2、PTGS2)的表达水平进行验证。
结果与结论：①肾阴阳两虚证组与健康对照组、肾阴虚证组、肾阳虚证组分别筛选出235，247，4 557个差异表达基因，3个比较组交集分析后筛选出肾阴阳两虚证组关联差异基因22个(18个上调、4个下调)；②qRT-PCR验证显示目标基因的上下调趋势与转录组测序结果一致；③基因本体论分析结果显示，生物学过程聚焦能量代谢(烟酰胺腺嘌呤二核苷酸合成与代谢)和生理稳态(产热、血压调控)，分子功能涉及免疫防御、代谢调控、炎症与信号传导、离子通道调节等；细胞组分与核糖体、内质网、细胞核及转运RNA修饰相关；④京都基因与基因组百科全书富集到60条通路，包括凋亡细胞清除、核因子κB、肿瘤坏死因子、白细胞介素17、血管内皮生长因子、叉头框蛋白O信号通路及代谢通路等；⑤提示肾阴阳两虚证绝经后骨质疏松症是多维度分子网络失衡的综合表现，与核糖体合成障碍、非编码RNA与信号转导及转录调控、免疫炎症调控及代谢转运相关。
https://orcid.org/0009-0004-5719-7470 (何艳艳) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 绝经后骨质疏松症, 肾阴阳两虚证, 差异基因, 转录组测序, 信号通路

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

中图分类号: