Periosteum progenitors could stimulate bone regeneration in aged murine bone defect model

Periosteal stem cells are critical for bone regeneration, while the numbers will decrease with age. This study focused on whether Prx1⁺ cell, a kind of periosteal stem cell, could stimulate bone regeneration in aged mice. Four weeks and 12 months old Prx1CreER-GFP; Rosa26^tdTomato mice were used to reveal the degree of Prx1⁺ cells participating in the femoral fracture healing procedure. One week, 8 weeks, 12 and 24 months old Prx1CreER-GFP mice were used to analyse the real-time distribution of Prx1⁺ cells. Twelve months old C57BL/6 male mice (n = 96) were used to create the bone defect model and, respectively, received hydrogel, hydrogel with Prx1^- mesenchymal stem cells and hydrogel with Prx1⁺ cells. H&E staining, Synchrotron radiation-microcomputed tomography and mechanical test were used to analyse the healing results. The results showed that tdTomato⁺ cells were involved in bone regeneration, especially in young mice. At the same time, GFP⁺ cells decreased significantly with age. The Prx1⁺ cells group could significantly improve bone regeneration in the murine bone defect model via directly differentiating into osteoblasts and had better osteogenic differentiation ability than Prx1^- mesenchymal stem cells. Our finding revealed that the quantity of Prx1⁺ cells might account for decreased bone regeneration ability in aged mice, and transplantation of Prx1⁺ cells could improve bone regeneration at the bone defect site.