Department of Joints, Tianjin Hospital, Tianjin University, 300211, China.
Clinical College of Orthopedics, Tianjin Medical University, Tianjin 300211, China.
Comput Math Methods Med. 2022 May 12;2022:4914727. doi: 10.1155/2022/4914727. eCollection 2022.
Disused osteoporosis is a kind of osteoporosis, a common age-related disease. Neurological disorders are major risk factors for osteoporosis. Though there are many studies on disuse osteoporosis, the genetic mechanisms for the association between glutathione metabolism and ferroptosis in osteoblasts with disuse osteoporosis are still unclear. The purpose of this study is to explore the key genes and other related mechanism of ferroptosis and glutathione metabolism in osteoblast differentiation and disuse osteoporosis. By weighted gene coexpression network analysis (WGCNA), the process of osteoblast differentiation-related genes was studied in GSE30393. And the related functional pathways were found through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. By combining GSE1367 and GSE100933 together, key genes which were separately bound up with glutathione metabolism and ferroptosis were located. The correlation of these key genes was analyzed by the Pearson correlation coefficient. GSTM1 targeted agonist glutathione (GSH) selected by connectivity map (CMap) analysis was used to interfere with the molding disused osteoporosis process in MC3T3-E1 cells. RT-PCR and intracellular reactive oxygen species (ROS) were performed. Two important pathways, glutathione metabolism and ferroptosis pathways, were found. GSTM1 and TFRC were thought as key genes in disuse osteoporosis osteoblasts with the two mechanisms. The two genes have a strong negative correlation. Our experiment results showed that the expression of TFRC was consistent with the negative correlation with the activation process of GSTM1. The strong relationship between the two genes was proved. Glutathione metabolism and ferroptosis are important in the normal differentiation of osteoblasts and the process of disuse osteoporosis. GSTM1 and TFRC were the key genes. The two genes interact with each other, which can be seen as a bridge between the two pathways. The two genes participate in the process of reducing ROS in disuse osteoporosis osteoblasts.
废用性骨质疏松症是一种骨质疏松症，是一种常见的与年龄相关的疾病。神经紊乱是骨质疏松症的主要危险因素。尽管有许多关于废用性骨质疏松症的研究，但谷胱甘肽代谢与成骨细胞中铁死亡在废用性骨质疏松症中的关联的遗传机制仍不清楚。本研究旨在探讨成骨细胞分化和废用性骨质疏松症中铁死亡和谷胱甘肽代谢的关键基因和其他相关机制。通过加权基因共表达网络分析（WGCNA），研究了 GSE30393 中成骨细胞分化相关基因的过程。并通过京都基因与基因组百科全书（KEGG）途径分析找到了相关的功能途径。通过将 GSE1367 和 GSE100933 结合在一起，找到了分别与谷胱甘肽代谢和铁死亡相关的关键基因。通过皮尔逊相关系数分析了这些关键基因的相关性。连接组分析（CMap）分析选择的谷胱甘肽（GSH）靶向激动剂 GSTM1 用于干扰 MC3T3-E1 细胞中废用性骨质疏松症形成过程。进行 RT-PCR 和细胞内活性氧（ROS）检测。发现了两个重要的途径，即谷胱甘肽代谢和铁死亡途径。GSTM1 和 TFRC 被认为是这两种机制下废用性骨质疏松症成骨细胞中的关键基因。这两个基因有很强的负相关。我们的实验结果表明，TFRC 的表达与 GSTM1 激活过程呈负相关，这两个基因之间的强相关性得到了证明。谷胱甘肽代谢和铁死亡在成骨细胞的正常分化和废用性骨质疏松症的发生过程中起着重要作用。GSTM1 和 TFRC 是关键基因。这两个基因相互作用，可以看作是两条途径之间的桥梁。这两个基因参与减少废用性骨质疏松症成骨细胞中 ROS 的过程。
