骨质疏松症和骨关节炎有什么共同之处？骨质疏松症和骨关节炎骨髓间充质干细胞中重叠差异表达基因的综合研究。
What do osteoporosis and osteoarthritis have in common? An integrated study of overlapping differentially expressed genes in bone mesenchymal stem cells of osteoporosis and osteoarthritis.
机构信息
Department of Orthopedics, Hai'an People's Hospital, Zhongba Road 17, Hai'an, Jiangsu 226600, China; Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu 215000, China.
Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu 215000, China.
出版信息
Gene. 2024 Jan 30;893:147914. doi: 10.1016/j.gene.2023.147914. Epub 2023 Oct 20.
OBJECTIVE
For identification of aberrantly expressed genes in mesenchymal stem cells of osteoporosis (OP) and osteoarthritis (OA), Gene Expression Omnibus (GEO) datasets were integrated to investigate the intersection point.
METHODS
GSE35958 (osteoporosis) and GSE19664 (osteoarthritis) datasets were obtained from GEO database. The abnormally expressed genes were analyzed by GEO2R. Functional enrichment was explored by Metascape database and R software. The String database and Cytoscape software were used to build the protein-protein interaction network and identify hub genes. GSE35957 and GSE116925 were used as verification datasets. Single-cell analysis and pseudotime analysis were undertaken. CTDbase, Network Analyst, HPA database, HERB database and MIRW database were used to research the information, tissue and cell distribution, regulation, interaction and ingredients targeting the hub genes. Additionally, in vitro experiments such as RT-PCR, ALP staining and immunofluorescence were undertaken as verification tests.
RESULTS
Ten hub genes were identified in this study. All these genes play an important role in bone or cartilage generation. They have diagnostic values and therapeutic potential for OA and OP. Single-cell analysis visualized the cell distribution and pseudotime distribution of these genes. Some potential therapeutic ingredients of these genes were identified, such as curcumin, wogonin and glycerin. In vitro experiments, RT-PCR results showed that COL9A3 and MMP3 were downregulated and PTH1R was upregulated during osteogenic induction of BMSC. Immunohistochemical results showed the expression trend of MMP3 and COL2A1.
CONCLUSION
Ten abnormal hub genes of osteoporosis and osteoarthritis were identified successfully by this study. They were important regulatory genes for healthy bone and cartilage. These genes could be the common connections between osteoporosis and osteoarthritis as well as treatment targets. Further study of the regulatory mechanism and treatment effects of these genes would be valuable. The results of this study could contribute to further research.
目的
通过整合基因表达综合数据库（GEO）数据集，鉴定骨质疏松症（OP）和骨关节炎（OA）骨髓间充质干细胞中异常表达的基因，以寻找两者的交集点。
方法
从 GEO 数据库中获取 GSE35958（骨质疏松症）和 GSE19664（骨关节炎）数据集。使用 GEO2R 分析异常表达基因。通过 Metascape 数据库和 R 软件进行功能富集分析。使用 String 数据库和 Cytoscape 软件构建蛋白质-蛋白质相互作用网络，并识别枢纽基因。使用 GSE35957 和 GSE116925 作为验证数据集。进行单细胞分析和拟时分析。使用 CTDbase、Network Analyst、HPA 数据库、HERB 数据库和 MIRW 数据库研究枢纽基因的信息、组织和细胞分布、调控、相互作用和作用靶点的成分。此外，还进行了 RT-PCR、碱性磷酸酶染色和免疫荧光等体外实验作为验证测试。
结果
本研究共鉴定出 10 个枢纽基因。这些基因在骨骼或软骨生成中均发挥着重要作用。它们对 OA 和 OP 具有诊断价值和治疗潜力。单细胞分析可视化了这些基因的细胞分布和拟时分布。鉴定出了这些基因的一些潜在治疗成分，如姜黄素、白杨素和甘油。体外实验结果显示，在 BMSC 成骨诱导过程中，COL9A3 和 MMP3 表达下调，而 PTH1R 表达上调。免疫组化结果显示 MMP3 和 COL2A1 的表达趋势。
结论
本研究成功鉴定出骨质疏松症和骨关节炎的 10 个异常枢纽基因。它们是健康骨骼和软骨的重要调控基因。这些基因可能是骨质疏松症和骨关节炎的共同联系，也是治疗靶点。进一步研究这些基因的调控机制和治疗效果将具有重要价值。本研究的结果可为进一步研究提供参考。
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