Heterogeneity of murine periosteum progenitors involved in fracture healing

• Published in: eLife Vol. 10
• Main Authors: Matthews, Brya G, Novak, Sanja, Sbrana, Francesca V, Funnell, Jessica L, Cao, Ye, Buckels, Emma J, Grcevic, Danka, Kalajzic, Ivo
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 09-02-2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Actin; alpha smooth muscle actin; Animals; Ataxin; Bone growth; Bone healing; Bone marrow; Cartilage; Chondrocytes; Comparative analysis; Female; Flow cytometry; fracture; Fracture Healing; Fractures; Histology; Male; Mice; Muscle proteins; osteoblast; Osteoblasts; Osteogenesis; pdgfra; Periosteum; Periosteum - physiology; Progenitor cells; skeletal stem cell; Smooth muscle; Stem cells; Stem Cells and Regenerative Medicine; mouse; stem cells; pdgfra; periosteum; regenerative medicine; skeletal stem cell; alpha smooth muscle actin; osteoblast; fracture
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.58534

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 (αSMA) 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 αSMACreER. 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.