Zhang W, Chu WH. Letter to the Editor: Sclerostin knockdown in human umbilical cord mesenchymal stem cells confers superior therapeutic efficacy against steroid-induced osteonecrosis. World J Stem Cells 2026; 18(7): 115076 [DOI: 10.4252/wjsc.115076]
Corresponding Author of This Article
Wen-Hui Chu, PhD, Associate Professor, School of Life Science, Taizhou University, No. 1139 Shifu Avenue, Jiaojiang District, Taizhou 318000, Zhejiang Province, China. jake-chu@hotmail.com
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Cell & Tissue Engineering
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letter
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Zhang W, Chu WH. Letter to the Editor: Sclerostin knockdown in human umbilical cord mesenchymal stem cells confers superior therapeutic efficacy against steroid-induced osteonecrosis. World J Stem Cells 2026; 18(7): 115076 [DOI: 10.4252/wjsc.115076]
World J Stem Cells. Jul 26, 2026; 18(7): 115076 Published online Jul 26, 2026. doi: 10.4252/wjsc.115076
Letter to the Editor: Sclerostin knockdown in human umbilical cord mesenchymal stem cells confers superior therapeutic efficacy against steroid-induced osteonecrosis
Wei Zhang, Wen-Hui Chu
Wei Zhang, Guangdong Eco-Engineering Polytechnic, Guangzhou 510520, Guangdong Province, China
Wen-Hui Chu, School of Life Science, Taizhou University, Taizhou 318000, Zhejiang Province, China
Author contributions: Chu WH and Zhang W contributed to the conceptualization; Chu WH contributed to the writing, reviewing and editing; Zhang W participated in the writing of the original draft; all authors participated in drafting the manuscript and have read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Wen-Hui Chu, PhD, Associate Professor, School of Life Science, Taizhou University, No. 1139 Shifu Avenue, Jiaojiang District, Taizhou 318000, Zhejiang Province, China. jake-chu@hotmail.com
Received: October 9, 2025 Revised: November 22, 2025 Accepted: January 26, 2026 Published online: July 26, 2026 Processing time: 288 Days and 13.2 Hours
Abstract
Mesenchymal stem cell-based therapies have emerged as promising candidates for the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). A study by Lv et al published in the recent issue of the World Journal of Stem Cells, investigated a novel strategy aimed at enhancing the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSCs) for SANFH through the genetic silencing of sclerostin (SOST), a key inhibitor of bone formation. In a murine model of SANFH, transplantation of SOST-silenced hUCMSCs yielded superior structural and histological outcomes compared with unmodified hUCMSCs. Micro-computed tomography confirmed marked restoration of the femoral head microarchitecture, including increased bone volume, trabecular number, and trabecular thickness. Histological examination revealed reduced adipocyte infiltration and fewer empty lacunae following SOST-silenced hUCMSCs treatment. Mechanistically, these improvements were associated with a shift in bone metabolism toward osteogenesis, reflected by an elevated serum osteoprotegerin/receptor activator of nuclear factor-kappa B ligand ratio, activation of the Wnt/β-catenin pathway, and downregulation of adipogenic markers (peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein) in bone tissue. Collectively, these findings demonstrate that SOST knockdown corrects the osteogenic-adipogenic imbalance by modulating the Wnt/β-catenin pathway, thereby significantly augmenting the therapeutic efficacy of hUCMSCs in SANFH. However, this approach warrants further translational studies.
Core Tip: This study demonstrates that sclerostin (SOST) gene silencing in human umbilical cord mesenchymal stem cells enhances their therapeutic efficacy in a steroid-induced osteonecrosis model. Genetically modified SOST-silenced human umbilical cord mesenchymal stem cells significantly improved bone microarchitecture, promoted osteogenic differentiation, and inhibited adipogenic formation by activating the Wnt/β-catenin pathway. This targeted approach effectively restored the bone metabolic balance, positioning SOST-silenced human umbilical cord mesenchymal stem cells as a promising advanced regenerative strategy for the treatment of steroid-induced femoral head necrosis.
