Skeletal Stem Cells: Origins, definitions, and functions in bone development and disease


 Skeletal stem cells (SSCs) are tissue-specific stem cells that can self-renew and sit at the apex of their differentiation hierarchy, giving rise to mature skeletal cell types required for bone growth, maintenance and repair. Dysfunction in SSCs is caused by stress conditions like ageing and inflammation and is emerging as a contributor to skeletal pathology, such as the pathogenesis of fracture nonunion. Recent lineage tracing experiments have shown that SSCs exist in the bone marrow, periosteum and resting zone of the growth plate. Unraveling their regulatory networks is crucial for understanding skeletal diseases and developing therapeutic strategies. In this review, we systematically introduce the definition, location, stem cell niches, regulatory signaling pathways, and clinical applications of SSCs.