Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells

Cell Stem Cell. 2019 Dec 5;25(6):784-796.e5. doi: 10.1016/j.stem.2019.11.003.


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+αSMA+ 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.

Keywords: CCL5; bone repair; in vivo real-time imaging; periosteum; skeletal stem cells; stem cell migration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Adolescent
  • Adult
  • Animals
  • Cell Movement / physiology
  • Child
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Myxovirus Resistance Proteins / genetics
  • Myxovirus Resistance Proteins / metabolism*
  • Periosteum / cytology*
  • Periosteum / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Young Adult


  • Actins
  • Myxovirus Resistance Proteins
  • alpha-smooth muscle actin, mouse