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Research Paper|Volume 12, Issue 11|pp 10473—10487

p53 plays a central role in the development of osteoporosis

Tao Yu1, Xiaomeng You2, Haichao Zhou1, Alex Kang3, Wenbao He1, Zihua Li1, Bing Li1, Jiang Xia1, Hui Zhu1, Youguang Zhao1, Guangrong Yu1, Yuan Xiong4, Yunfeng Yang1
  • 1Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
  • 2Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • 3Center for Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
  • 4Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
* Equal contribution
Received: February 17, 2020Accepted: April 20, 2020Published: June 2, 2020
https://doi.org/10.18632/aging.103271

Copyright © 2020 Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 TP53, MAPK1, CASP3, CTNNB1, CCND1, NOTCH1, CDK1, IGF1, ERBB2, CYCS 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 TP53 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.