Sclerostin silencing in human umbilical cord mesenchymal stem cells enhances bone regeneration <i>via</i> Wnt pathway activation

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 <i>et al</i> explores the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs) genetically modified to silence sclerostin, a known inhibitor of bone formation <i>via</i> 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.