Other
12 Authors
- Lei K,
- Park D,
- Rosenfeld SB,
- Lee B,
- Wang H,
- Scadden DT,
- Ortinau LC,
- Lee D,
- Jeong Y,
- Hara Y,
- Grafe I,
- Deveza L
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. |