Periosteal Skeletal Stem and Progenitor Cells in Bone Regeneration.

Several markers have been described for pSSPCs but lack tissue specificity. In vivo lineage tracing and transcriptomic analyses have improved our understanding of pSSPC functions during bone regeneration. Bone injury activates pSSPCs that migrate, proliferate, and have the unique potential to form both bone and cartilage. The injury response of pSSPCs is controlled by many signaling pathways including BMP, FGF, Notch, and Wnt, their metabolic state, and their interactions with the blood clot, nerve fibers, blood vessels, and macrophages in the fracture environment. Periosteal SSPCs are essential for bone regeneration. Despite recent advances, further studies are required to elucidate pSSPC heterogeneity and plasticity that make them a central component of the fracture healing process and a prime target for clinical applications.