Characterization and role exploration of ferroptosis-related genes in osteoarthritis

Xinyu Wang; Tianyi Liu; Cheng Qiu; Shunan Yu; Yanzhuo Zhang; Yueyang Sheng; Chengai Wu

doi:10.3389/fmolb.2023.1066885

Characterization and role exploration of ferroptosis-related genes in osteoarthritis

Front Mol Biosci. 2023 Mar 6:10:1066885. doi: 10.3389/fmolb.2023.1066885. eCollection 2023.

Authors

Xinyu Wang¹, Tianyi Liu², Cheng Qiu³, Shunan Yu¹, Yanzhuo Zhang¹, Yueyang Sheng¹, Chengai Wu¹

Affiliations

¹ Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing, China.
² Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.

Abstract

Osteoarthritis (OA), viewing as a degenerative aseptic inflammatory disease, is characterized by joint pain and inflammation that significantly affects the quality of patients' life, especially for the elder. Although rapid progress has been achieved in elucidating the underlying mechanisms of OA occurrence and progression, there is still a lack of effective clinical therapeutics for OA patients. Currently the most common treatments including drug therapy and surgical operations are not very satisfactory in majority of cases, so it is worthy to explore new remedies. During the past few decades, a number of novel forms of regulated cell death have been reported widely, typified by ferroptosis, with its prominent features including reactive oxygen species (ROS) elevation, lipid peroxidation, iron accumulation and glutathione deprivation. Our study was designed to identify the functional roles of differentially expressed ferroptosis-related genes in OA, which were screened out by referring to GEO database via bioinformatics analyses. Human chondrocytes were applied to validate the above findings in the scenario of ferroptosis inhibitors administration. Results partially proved the consistency with bioinformatics analyses that ATF3 and TFRC were highly expressed in interleukin-1β (IL-1β)-stimulated chondrocytes whereas CXCL2 and JUN were downregulated. Besides, TFRC was firstly validated to be upregulated in IL-1β-stimulated chondrocytes, which could be reversed by ferroptosis inhibitors. In conclusion, our study reported two prominent ferroptosis-related genes, ATF3 and TFRC are upregulated in IL-1β-stimulated chondrocytes while CXCL2 and JUN are downregulated. And preliminary results demonstrated that TFRC might serve as an accomplice of ferroptosis process in IL-1β-stimulated chondrocytes and ferroptosis inhibitors have the potential to inhibit ROS in IL-1β-stimulated chondrocytes.

Keywords: ATF3; CXCl2; IL-1β; JUN; TFRC; chondrocyte; ferroptosis; osteoarthritis.

Grants and funding

This study was supported by National Natural Science Foundation of China (Grant No.81472139) and Beijing Municipal Health Commission (Grant no. BMHC-2019-9 and BMHC-2021-6).