Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Aging (Albany NY). 2020 Jun 2;12(11):10473-10487. doi: 10.18632/aging.103271.
Osteoporosis is a metabolic disease affecting 40% of postmenopausal women. It is characterized by decreased bone mass per unit volume and increased risk of fracture. We investigated the molecular mechanism underlying osteoporosis by identifying the genes involved in its development. Osteoporosis-related genes were identified by analyzing RNA microarray data in the GEO database to detect genes differentially expressed in osteoporotic and healthy individuals. Enrichment and protein interaction analyses carried out to identify the hub genes among the deferentially expressed genes revealed , , , , , , , , , to be the top 10 hub genes. In addition, p53 had the highest degree score in the protein-protein interaction network. In vivo and in vitro experiments showed that gene expression and serum p53 levels were upregulated in osteoporotic patients and a mouse osteoporosis model. The elevated p53 levels were associated with decreases in bone mass, which could be partially reversed by knocking down p53. These findings suggest p53 may play a central role in the development of osteoporosis.
骨质疏松症是一种影响 40%绝经后妇女的代谢性疾病。其特征是单位体积骨量减少,骨折风险增加。我们通过鉴定与骨质疏松症发生相关的基因,研究了骨质疏松症的分子机制。通过分析 GEO 数据库中的 RNA 微阵列数据,鉴定了骨质疏松症相关基因,以检测骨质疏松症患者和健康个体中差异表达的基因。进行富集和蛋白质相互作用分析,以鉴定差异表达基因中的枢纽基因,结果显示,、、、、、、、、、为前 10 个枢纽基因。此外,蛋白质-蛋白质相互作用网络中 p53 的度数得分最高。体内和体外实验表明,骨质疏松症患者和小鼠骨质疏松模型中基因表达和血清 p53 水平上调。升高的 p53 水平与骨量减少有关,p53 敲低可部分逆转这一现象。这些发现表明 p53 可能在骨质疏松症的发生发展中发挥核心作用。