World J Stem Cells. Feb 26, 2026; 18(2): 114980 Published online Feb 26, 2026. doi: 10.4252/wjsc.v18.i2.114980
Sclerostin silencing in human umbilical cord mesenchymal stem cells enhances bone regeneration via Wnt pathway activation
Prashasti Sharma, Dharmendra Kumar Maurya
Prashasti Sharma, Dharmendra Kumar Maurya, Life Sciences, Homi Bhabha National Institute, Mumbai 400094, Maharashtra, India
Prashasti Sharma, Dharmendra Kumar Maurya, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, Maharashtra, India
Author contributions: Sharma P has done a review of the literature, and drawn the scheme; Maurya DK has written the editorial.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Dharmendra Kumar Maurya, PhD, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, 3-82-S, A-Block, Modular Laboratory, Mumbai 400085, Maharashtra, India. dkmaurya@barc.gov.in
Received: October 11, 2025 Revised: November 10, 2025 Accepted: January 15, 2026 Published online: February 26, 2026 Processing time: 133 Days and 22.9 Hours
Abstract
Steroid-induced avascular necrosis of the femoral head is a debilitating condition caused by prolonged glucocorticoid exposure, leading to bone death and disrupted metabolism. Current treatment options are limited, especially in late-stage disease, emphasizing the urgent need for novel regenerative therapies. This study by Lv et al explores the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs) genetically modified to silence sclerostin, a known inhibitor of bone formation via the Wnt/β-catenin pathway. The authors engineered sh-human umbilical cord MSCs and demonstrated their enhanced osteogenic differentiation and suppression of adipogenesis compared to unmodified MSCs in a steroid-induced rat model of femoral head necrosis. Significant improvements were observed in bone microarchitecture, biochemical markers of bone metabolism, and histological parameters. This investigation suggests that sclerostin silencing enhances MSC efficacy by activating Wnt signaling, thereby offering a promising regenerative strategy for steroid-induced avascular necrosis of the femoral head that targets the core imbalance in bone remodeling.
Core Tip: Silencing sclerostin in human umbilical cord mesenchymal stem cells enhances their bone-regenerative potential by activating the Wnt/β-catenin signaling pathway, providing a novel therapeutic approach for steroid-induced avascular necrosis of the femoral head. In the study by Lv et al, sh-human umbilical cord mesenchymal stem cells demonstrated better osteogenesis, suppressed adipogenesis, and improved bone architecture in a steroid-induced rat model compared to unmodified cells.
