小桶
TLR2型
基因
生物
计算生物学
基因表达
信号转导
遗传学
生物信息学
转录组
TLR4型
作者
Dan Liu,Fangming Cao,Dian Liu,Hao Li,Lin Tao,Yue Zhu
出处
期刊:Bone and Joint Research
[British Editorial Society of Bone and Joint Surgery]
日期:2024-10-16
卷期号:13 (10): 573-587
标识
DOI:10.1302/2046-3758.1310.bjr-2023-0366.r1
摘要
Aims This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Methods Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes. Results WGCNA revealed critical gene modules for OB and OP, identifying the Toll-like receptor ( TLR ) signalling pathway as a common factor. TLR2 was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development. Conclusion Our study underscores the pivotal role of TLR2 in connecting OP and OB. It highlights the influence of TLR2 in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose TLR2 as a potential dual therapeutic target for treating OP and OB. Cite this article: Bone Joint Res 2024;13(10):573–587.
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