Lv H, Zheng CF, Chen XY, Wei JH, Tao YZ, Feng L, Feng Z, Lu SJ. Sclerostin-silenced human umbilical cord mesenchymal stem cells ameliorate bone metabolism in steroid-induced femoral head necrosis. World J Stem Cells 2025; 17(10): 110190 [DOI: 10.4252/wjsc.v17.i10.110190]
Corresponding Author of This Article
Shi-Jin Lu, Full Professor, Centre for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, No. 10 Huadong Road, Xingning District, Nanning 530000, Guangxi Zhuang Autonomous Region, China. jzwklu@163.com
Research Domain of This Article
Orthopedics
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Oct 26, 2025; 17(10): 110190 Published online Oct 26, 2025. doi: 10.4252/wjsc.v17.i10.110190
Sclerostin-silenced human umbilical cord mesenchymal stem cells ameliorate bone metabolism in steroid-induced femoral head necrosis
He Lv, Cai-Fang Zheng, Xing-Yu Chen, Ji-Hu Wei, Yi-Zi Tao, Lin Feng, Zhe Feng, Shi-Jin Lu
He Lv, Department of Massage, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
He Lv, Xing-Yu Chen, Yi-Zi Tao, Lin Feng, Faculty of Postgraduate, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Cai-Fang Zheng, Department of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Ji-Hu Wei, Zhe Feng, Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Shi-Jin Lu, Centre for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Co-corresponding authors: Zhe Feng and Shi-Jin Lu.
Author contributions: Feng Z and Lu SJ contributed equally to this work and are co-corresponding authors. Lv H and Lu SJ conceived the idea and designed the study; Zheng CF, Chen XY, Wei JH, Tao YZ, and Feng L contributed to the literature review and integrated the materials; Lv H and Chen XY prepared the draft; Feng Z and Lu SJ revised the manuscript and approved the final version. All the authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82260944; and the Key Research and Development Programs of Guangxi, No. 2021AB09011.
Institutional animal care and use committee statement: The research was reviewed and approved by the Animal Ethics Committee of Guangxi University of Traditional Chinese Medicine, No. DW20220408-053.
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: No additional data is available.
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: Shi-Jin Lu, Full Professor, Centre for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, No. 10 Huadong Road, Xingning District, Nanning 530000, Guangxi Zhuang Autonomous Region, China. jzwklu@163.com
Received: June 4, 2025 Revised: July 1, 2025 Accepted: September 22, 2025 Published online: October 26, 2025 Processing time: 146 Days and 21.9 Hours
Core Tip
Core Tip: In this study, we developed a multi-target gene silencing strategy against sclerostin (SOST), a negative regulator of bone formation, using RNA interference technology. We established a cellular model of human umbilical cord mesenchymal stem cells (hUCMSCs) with SOST-silenced (sh-hUCMSCs) with SOST gene silencing and compared the therapeutic effects of hUCMSCs and sh-hUCMSCs in a mouse model of steroid-induced avascular necrosis of the femoral head. Compared with hUCMSCs, sh-hUCMSCs more effectively inhibited adipogenic differentiation, promoted new bone formation, and improved trabecular bone parameters such as bone volume, trabecular number, and thickness, while reducing trabecular separation. Additionally, sh-hUCMSCs modulated the expression of key bone metabolic factors, including increased levels of osteoprotegerin and decreased levels of receptor activator of nuclear factor kappa B ligand and peroxisome proliferator-activated receptor gamma. These results suggest that silencing SOST enhances the osteogenic capacity and regenerative efficacy of hUCMSCs.
