Abstract
Background: Glucocorticoids (GCs) are critical regulatory molecules in the body, commonly utilized in clinical practice for their potent anti-inflammatory and immunosuppressive properties. However, prolonged, high-dose GC therapy is frequently associated with femoral head necrosis, a condition known as glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Emerging evidence suggests that enhanced autophagy may mitigate apoptosis, thereby protecting osteoblasts from GC-induced damage and delaying the progression of ONFH. This study aims to evaluate whether human umbilical cord mesenchymal stem cells (hUCMSCs) can alleviate GC-induced osteoblast injury through autophagy modulation. Methods: In vitro, osteoblasts were exposed to GCs for 48 h, followed by co-culture with hUCMSCs for an additional 12 h before further analysis. The osteoblasts were categorized into four experimental groups: (A) control group, (B) Dex group, (C) Dex + hUCMSC group, and (D) Dex + hUCMSC + 3-MA group. In vivo, rabbits were assigned to one of four groups: Con, MPS, core decompression (CD), and CD + hUCMSC (n = 12 per group), and subsequently subjected to CT imaging and HE staining. Results: In vitro results demonstrate that hUCMSC treatment mitigated GC-induced osteoblast apoptosis and preserved osteogenic activity through autophagy modulation. In vivo, infusion of hUCMSCs enhanced trabecular thickness in the femoral head and improved the femoral head microenvironment. Conclusions: These findings suggest that hUCMSCs protect osteoblasts from GC-induced damage by regulating autophagy, offering new insights into the potential therapeutic use of hUCMSCs for treating ONFH via autophagy enhancement.