Publication Name	World Journal of Stem Cells
Manuscript ID	110190
Country	China

Category	Orthopedics
Manuscript Type	Basic Study
Article Title	Sclerostin-silenced human umbilical cord mesenchymal stem cells ameliorate bone metabolism in steroid-induced femoral head necrosis
Manuscript Source	Unsolicited Manuscript
All Author List	He Lv, Cai-Fang Zheng, Xing-Yu Chen, Ji-Hu Wei, Yi-Zi Tao, Lin Feng, Zhe Feng and Shi-Jin Lu
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China 82260944 Key Research and Development Programs of Guangxi 2021AB09011
Corresponding Author	Shi-Jin Lu, Full Professor, 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
Key Words	Genetic modification; Human umbilical cord mesenchymal stem cells; Steroid-induced avascular necrosis of the femoral head; Sclerostin; Bone metabolism; Wnt signaling pathway; RNA interference
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.
Citation	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; In press

Received	2025-06-04 03:06
Peer-Review Started	2025-06-04 03:06
To Make the First Decision
Return for Revision	2025-06-18 02:26
Revised	2025-07-01 17:58
Second Decision	2025-09-15 00:25
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-09-22 07:29
Articles in Press	2025-09-22 07:29
Publication Fee Transferred	2025-07-04 07:42
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ISSN	1948-0210 (online)
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