Heterogeneity of murine periosteum progenitors involved in fracture healing

The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched with progenitor cells, including Sca1(+) cells, fibroblast colony-forming units, and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that alpha smooth muscle actin (alpha SMA) identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture can be targeted by alpha SMACreER. Previously identified skeletal stem cell populations were common in periosteum but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched with skeletal progenitor cells, and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

Automated summary

The periosteum is found to be highly enriched with progenitor cells, including alpha SMA-identified osteochondroprogenitors critical for bone formation during fracture healing. Additionally, Col2.3CreER-labeled osteoblast cells contribute to osteoblasts but not chondrocytes in fracture healing, and most periosteal osteochondroprogenitors can be targeted using alpha SMACreER.