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Publication : Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells.

First Author  Ortinau LC Year  2019
Journal  Cell Stem Cell Volume  25
Issue  6 Pages  784-796.e5
PubMed ID  31809737 Mgi Jnum  J:307129
Mgi Id  MGI:6710886 Doi  10.1016/j.stem.2019.11.003
Citation  Ortinau LC, et al. (2019) Identification of Functionally Distinct Mx1+alphaSMA+ Periosteal Skeletal Stem Cells. Cell Stem Cell 25(6):784-796.e5
abstractText  The periosteum is critical for bone maintenance and healing. However, the in vivo identity and specific regulatory mechanisms of adult periosteum-resident skeletal stem cells are unknown. Here, we report animal models that selectively and durably label postnatal Mx1+alphaSMA+ periosteal stem cells (P-SSCs) and establish that P-SSCs are a long-term repopulating, functionally distinct SSC subset responsible for lifelong generation of periosteal osteoblasts. P-SSCs rapidly migrate toward an injury site, supply osteoblasts and chondrocytes, and recover new periosteum. Notably, P-SSCs specifically express CCL5 receptors, CCR3 and CCR5. Real-time intravital imaging revealed that the treatment with CCL5 induces P-SSC migration in vivo and bone healing, while CCL5/CCR5 deletion, CCR5 inhibition, or local P-SSC ablation reduces osteoblast number and delays bone healing. Human periosteal cells express CCR5 and undergo CCL5-mediated migration. Thus, the adult periosteum maintains genetically distinct SSC subsets with a CCL5-dependent migratory mechanism required for bone maintenance and injury repair.
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