Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2024; 15(5): 977-987
Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.977
Polycytosine RNA-binding protein 1 regulates osteoblast function via a ferroptosis pathway in type 2 diabetic osteoporosis
Hong-Dong Ma, Lei Shi, Hai-Tian Li, Xin-Dong Wang, Mao-Wei Yang
Hong-Dong Ma, Lei Shi, Department of Orthopedics, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Hai-Tian Li, Xin-Dong Wang, Mao-Wei Yang, Department of Orthopedics, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Co-first authors: Hong-Dong Ma and Lei Shi.
Author contributions: Yang MW conceptualized and designed the study; Ma HD and Shi L performed the study and acquired the data, and drafted the manuscript; Li HT and Wang XD analyzed and interpreted the data; Yang MW and Ma HD confirmed the authenticity of the raw data; All authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81471094 and No. 82202743.
Institutional review board statement: This study was approved by Ethics Committee of Nantong University [approval No. 2023-K185-01].
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mao-Wei Yang, MD, Chief Doctor, Professor, Department of Orthopedics, The First Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang 110001, Liaoning Province, China. mwyang@cmu.edu.cn
Received: December 19, 2023
Peer-review started: December 19, 2023
First decision: January 9, 2024
Revised: January 22, 2024
Accepted: March 15, 2024
Article in press: March 15, 2024
Published online: May 15, 2024
Processing time: 143 Days and 10.1 Hours
Abstract
BACKGROUND

Recently, type 2 diabetic osteoporosis (T2DOP) has become a research hotspot for the complications of diabetes, but the specific mechanism of its occurrence and development remains unknown. Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP. Polycytosine RNA-binding protein 1 (PCBP1), an iron ion chaperone, is considered a protector of ferroptosis.

AIM

To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.

METHODS

A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose (HG) and/or ferroptosis inhibitors at different concentrations and times. Transmission electron microscopy was used to examine the morphological changes in the mitochondria of osteoblasts under HG, and western blotting was used to detect the expression levels of PCBP1, ferritin, and the ferroptosis-related protein glutathione peroxidase 4 (GPX4). A lentivirus silenced and overexpressed PCBP1. Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin (OPG) and osteocalcin (OCN), whereas flow cytometry was used to detect changes in reactive oxygen species (ROS) levels in each group.

RESULTS

Under HG, the viability of osteoblasts was considerably decreased, the number of mitochondria undergoing atrophy was considerably increased, PCBP1 and ferritin expression levels were increased, and GPX4 expression was decreased. Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1, increased the expression levels of ferritin, GPX4, OPG, and OCN, compared with the HG group. Flow cytometry results showed a reduction in ROS, and an opposite result was obtained after silencing PCBP1.

CONCLUSION

PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment. Moreover, PCBP1 may be a potential therapeutic target for T2DOP.

Keywords: Polycytosine RNA-binding protein 1; Ferroptosis; Reactive oxygen species; Ferritin; Osteoblast; Type 2 diabetic osteoporosis

Core Tip: Type 2 diabetic osteoporosis (T2DOP) is one of the most common complications of type 2 diabetes and its incidence has increased annually to seriously affect human health. T2DOP has a complicated environment and pathogenesis, including high glucose (HG) toxicity, inflammatory response, and iron metabolism disorders. However, the molecular mechanisms underlying T2DOP remain unclear. This study demonstrated that polycytosine RNA-binding protein 1 (PCBP1) protects osteoblasts and reduces the damage caused by ferroptosis by promoting ferritin expression in a HG environment in T2DOP, suggesting the promising therapeutic potential of PCBP1 in T2DOP.