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在微重力相关废用性骨质疏松中调节间充质干细胞成骨或成脂的粘着斑内潜在关键基因：一项综合分析

The potential key genes within focal adhesion that regulate mesenchymal stem cells osteogenesis or adipogenesis in microgravity related disuse osteoporosis: an integrated analysis.

作者信息

Zhao Haoyang, Tu Xiaolin

机构信息

Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

出版信息

Front Endocrinol (Lausanne). 2025 Mar 10;16:1469400. doi: 10.3389/fendo.2025.1469400. eCollection 2025.

DOI:10.3389/fendo.2025.1469400
PMID:40130165
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11930814/
Abstract

This study aimed to identify key genes related to focal adhesions (FA) and cells involved in osteoblast (OS) and adipocyte (AD) differentiation in osteoporosis. A mouse model of disuse osteoporosis was made by hindlimbs unloading (HLU)/Tail - suspension. Micro - CT and histological analysis were done, and differentially expressed genes (DEGs) from GSE100930 were analyzed. Soft clustering on GSE80614 OS/AD samples found FA - related candidate genes. protein-protein interaction (PPI) network and cytoHubba's Degree algorithm identified key FA - genes, validated by quantitative polymerase chain reaction (qPCR). Key OS/AD - associated cells were identified by single - cell analysis. The mouse model showed decreased bone density, microstructure damage, increased marrow adiposity, and altered gene expression. Key FA - related genes for osteogenesis (ITGB3, LAMC1, COL6A3, ITGA8, PDGFRB) and adipogenesis (ITGB3, ITGA4, LAMB1, ITGA8, LAMA4) were found and validated. Key cells (chondrocyte, adipocyte, and osteoblast progenitors) are involved in specific pathways, with osteoblast progenitors having stronger interactions. Pseudotime analysis implies differentiation from chondrocyte progenitors to adipocyte, then osteoblast progenitors. This study provides new insights for disuse osteoporosis research.

摘要

本研究旨在确定与骨质疏松症中粘着斑（FA）以及参与成骨细胞（OS）和脂肪细胞（AD）分化的细胞相关的关键基因。通过后肢卸载（HLU）/尾部悬吊建立废用性骨质疏松症小鼠模型。进行了显微CT和组织学分析，并分析了来自GSE100930的差异表达基因（DEG）。对GSE80614 OS/AD样本进行软聚类，发现了与FA相关的候选基因。蛋白质-蛋白质相互作用（PPI）网络和CytoHubba的度算法确定了关键的FA基因，并通过定量聚合酶链反应（qPCR）进行了验证。通过单细胞分析确定了关键的OS/AD相关细胞。小鼠模型显示骨密度降低、微观结构损伤、骨髓脂肪增多以及基因表达改变。发现并验证了与成骨相关的关键FA基因（ITGB3、LAMC1、COL6A3、ITGA8、PDGFRB）和与脂肪生成相关的关键FA基因（ITGB3、ITGA4、LAMB1、ITGA8、LAMA4）。关键细胞（软骨细胞、脂肪细胞和成骨祖细胞）参与特定途径，其中成骨祖细胞具有更强的相互作用。伪时间分析表明从软骨祖细胞分化为脂肪细胞，然后再分化为骨祖细胞。本研究为废用性骨质疏松症的研究提供了新的见解。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb1/11930814/28e61e015571/fendo-16-1469400-g008.jpg
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