Age Related Tissue Fibrosis During Fracture Repair Is Mediated by Wnt/β-catenin Signaling

• Main Author: Silkstone, David
• Other Authors: Benjamin, Alman
• Language: en_ca
• Published: 2010
• Subjects: Fracture Repair; Elderly; Osteoblasts; Tissue Fibrosis; Wnt/β-catenin Signaling; Multipotent Mesenchymal Stem Cells; 0433; 0410; 0379
• Online Access: http://hdl.handle.net/1807/25802

The regenerative potential of tissue injury declines with age. Recently, a significant role for Wnt/β-catenin signaling has been shown in tissue specific stem cell aging, leading to increased tissue fibrosis. Wnt/β-catenin signaling regulates the differentiation of multipotent mesenchymal stem cells into osteoblasts during fracture repair. We investigated the potential role of dysregulated Wnt/β-catenin signaling in delayed fracture union and tissue fibrosis in the elderly. Old mice displayed increased total β-catenin protein levels at 4 and 7 days post-fracture and tissue fibrosis at 14 and 21 days post-fracture compared to young mice. Furthermore, treatment with a pharmalogical agent decreased total β-catenin protein levels in the fracture callus at 4 days post-fracture and prevented tissue fibrosis at 21 days post-fracture. Our data suggests that dysregulated Wnt/β-catenin signaling in the elderly contributes to delayed fracture repair and tissue fibrosis and offers a potential therapeutic strategy to improve fracture outcome in the elderly.