Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2025; 17(3): 98911
Published online Mar 26, 2025. doi: 10.4252/wjsc.v17.i3.98911
Fat mass and obesity-associated protein in mesenchymal stem cells inhibits osteoclastogenesis via lnc NORAD/miR-4284 axis in ankylosing spondylitis
Wen-Jie Liu, Jia-Xin Wang, Quan-Feng Li, Yun-Hui Zhang, Peng-Fei Ji, Jia-Hao Jin, Yi-Bin Zhang, Zi-Hao Yuan, Pei Feng, Yan-Feng Wu, Hui-Yong Shen, Peng Wang
Wen-Jie Liu, Jia-Xin Wang, Quan-Feng Li, Yun-Hui Zhang, Peng-Fei Ji, Jia-Hao Jin, Yi-Bin Zhang, Zi-Hao Yuan, Hui-Yong Shen, Peng Wang, Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
Wen-Jie Liu, Jia-Xin Wang, Quan-Feng Li, Yun-Hui Zhang, Peng-Fei Ji, Jia-Hao Jin, Yi-Bin Zhang, Zi-Hao Yuan, Pei Feng, Yan-Feng Wu, Hui-Yong Shen, Peng Wang, Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
Pei Feng, Yan-Feng Wu, Center for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
Co-first authors: Wen-Jie Liu and Jia-Xin Wang.
Co-corresponding authors: Hui-Yong Shen and Peng Wang.
Author contributions: Liu WJ and Wang JX conducted the experiments and investigation and contributed equally to this work as co-first authors. Liu WJ, Wang JX, and Li QF contributed to the conceptualization and methodology of this study; Ji PF, Jin JH, Zhang YB, and Yuan ZH were involved in the data curation and analysis of this manuscript; Liu WJ and Li QF wrote the original draft; Zhang YH and Feng P participated in the writing - review & editing; Wu YF, Shen HY, and Wang P were involved in the resources and supervision and funding acquisition. Shen HY and Wang P designed the research and approved the final version of the manuscript as co-corresponding authors of this manuscript.
Supported by Guangdong Provincial Clinical Research Center for Orthopedic Diseases, No. 2023B110001; the Excellent Medical Innovation Talent Program of the Eighth Affiliated Hospital of Sun Yat-sen University, No. YXYXCXRC202101; the National Natural Science Foundation of China, No. 82172349, No. 82372372, No. 22105229, No. 32170708, No. 82102530, No. 82102541, No. 82103098, No. 82103909, No. 82104182, No. 82104350, No. 82170427, No. 82171291, No. 82172215, No. 82172385, and No. 82302661; Guangdong Natural Science Foundation, No. 2023A1515010568 and No. 2021A1515111057; Shenzhen Science and Technology Program, No. JCYJ20220530144201004 and No. RCBS20210609104445097; and Futian Healthcare Research Project, No. FTWS2022022, No. FTWS2021013, No. FTWS2023072, and No. FTWS2022047.
Institutional review board statement: The collection of human specimens and the experiments with human specimens were approved by the Ethics Committee of the Eighth Affiliated Hospital, Sun Yat-sen University. The approval numbers for handling human subjects were 2021r171.
Institutional animal care and use committee statement: The animal experimentation protocols received approval from the Ethics Committee of the Eighth Affiliated Hospital, Sun Yat-Sen University. The assigned approval number for the experiments was SYSU-IACUC-2022-001060.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data findings are provided in this study, and raw data can be requested from the corresponding author upon 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: Peng Wang, PhD, Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, No. 3025 Shennan Road, Shenzhen 518033, Guangdong Province, China. wangp57@mail.sysu.edu.cn
Received: July 9, 2024
Revised: January 3, 2025
Accepted: February 26, 2025
Published online: March 26, 2025
Processing time: 254 Days and 22.7 Hours
Core Tip

Core Tip: This study explores how mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients inhibit osteoclastogenesis. We observed higher expression of fat mass and obesity-associated protein (FTO) in AS-MSCs compared to healthy controls. Reducing FTO expression diminished their osteoclast inhibitory effect. FTO regulates the long non-coding RNA activated by DNA damage (NORAD) by modulating its N6-methyladenosine methylation, and NORAD silencing increased osteoclast formation via miR-4284. These results highlight FTO as a key regulator of AS-MSC function and suggest the long noncoding RNA NORAD/miR-4284 axis as a novel mechanism of osteoclast inhibition in AS.