Identification of the molecular link: STAT3 is a shared key gene linking postmenopausal osteoporosis and sarcopenia.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING
Dian Liu, Ke Wang, Jinpeng Wang, Fangming Cao, Lin Tao
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引用次数: 0

Abstract

Aims: This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods: We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.

Results: Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation.

Conclusion: STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases.

确定分子联系:STAT3 是连接绝经后骨质疏松症和肌肉疏松症的共同关键基因。
目的:本研究探讨了绝经后骨质疏松症(POMP)和肌肉疏松症之间的共同遗传特征和分子相互作用。我们假设这两种运动系统疾病在病理生理学和调控机制方面存在重叠:方法:我们使用加权基因共表达网络分析(WGCNA)、机器学习和京都基因与基因组百科全书(KEGG)富集分析法分析了基因表达总库(GEO)数据库中的微阵列数据,以确定 POMP 和肌肉疏松症之间的共同遗传因素。通过新队列中的差异基因表达进行了进一步验证。单细胞分析确定了高表达细胞亚群,其中包括骨质疏松症中的单核巨噬细胞和肌肉疏松症中的肌肉干细胞。竞争性内源性 RNA 网络提示了这些基因的调控元件:结果:信号转导和转录激活因子 3(STAT3)在两种情况下都有显著表达。单细胞分析确定了 STAT3 高表达的特定细胞,microRNA(miRNA)-125a-5p 成为潜在的调控因子。实验证实了 STAT3 在破骨细胞分化和肌肉增殖中的关键作用:结论:STAT3 已成为 POMP 和肌肉疏松症的关键基因。结论:STAT3 已成为 POMP 和肌肉疏松症的关键基因,这一观点将 STAT3 定位为潜在的共同治疗靶点,从而有可能改善这些与年龄相关疾病的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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