Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 24, Issue 20, Pages 12199-12210Publisher
WILEY
DOI: 10.1111/jcmm.15891
Keywords
aged mice; bone defect; bone regeneration; periosteum derived cells; Prx1(-)MSC; Prx1(+)MSC
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Funding
- National Natural Science Foundation of China [81730068]
- Fundamental Research Funds for the Central Universities of Central South University [2018dcyj074]
- Science and Technology Commission of Hunan Province of China [2017SK2061]
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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.
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