Skeletal stem cells, a new direction for the treatment of bone and joint diseases.

Skeletal stem cells (SSCs) are tissue-specific stem cells characterized by their capacity for self-renewal and their position at the apex of the differentiation hierarchy. They can generate mature bone cell types essential for bone development, maintenance, and repair. Lineage tracing experiments have demonstrated that SSCs reside in the bone marrow, periosteum, and the resting zone of the growth plate. These findings not only enhance our understanding of bone growth and development mechanisms but also offer novel therapeutic strategies for conditions such as epiphyseal injuries, fractures, osteoarthritis (OA), and other orthopedic diseases. Recent advancements in biological scaffold technology, combined with 3D printing techniques, have facilitated bone tissue regeneration using bone stem cells. In OA, SSCs antagonize inflammatory factors, such as tumor necrosis factor-alpha and interleukin-1 beta, via paracrine secretion of insulin-like growth factor 1 and transforming growth factor-beta. Simultaneously, SSCs secrete matrix metalloproteinase inhibitors to maintain cartilage matrix homeostasis. In femoral head necrosis, SSCs promote angiogenesis by secreting vascular endothelial growth factor and optimize the repair microenvironment through immune regulation, such as by inhibiting the nuclear factor-kappa B pathway. Additionally, bone stem cells have shown promise in cartilage regeneration therapy, particularly in treating degenerative diseases like OA and articular cartilage damage, thereby improving joint function. This review summarizes the latest research progress on the role of skeletal stem cells in bone and joint injury regeneration and provides new insights into potential therapeutic approaches.