Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments
Research & Innovation | May 10, 2023
Author/s: Jea Giezl N. Solidum, Youngjae Jeong, Francisco Heralde III, and Dongsu Park
Distinct Skeletal stem/progenitor cells (SSPCs), have recently been identified in skeletal compartments other than the bone marrow, such as the growth plate, periosteum, and calvarial sutures. Differences in the cellular and matrix environment of distinct SSPC populations are believed to regulate their stemness and to direct their roles at different stages of development, homeostasis, and regeneration; differences in embryonic origin and adjacent tissue structures also affect SSPC regulation. As these SSPC niches are dynamic and
highly specialized, changes under stress conditions and with aging can alter the cellular composition and molecular mechanisms in place, contributing to the dysregulation of local SSPCs and their activity in bone regeneration. In this review, we summarize the current scientific advances made in the study of the differential regulation pathways for distinct SSPCs in different bone compartments. We also discuss the physical, biological, and molecular factors that affect each skeletal compartment niche. Although some essential molecular regulators are shared by distinct SSPCs, their effect on differentiation, cell fate, or tissue type formation of distinct SSPCs can be different, directing the differences in rate of injury healing. Lastly, we look into how aging influences the regenerative capacity of SSPCs. Advancements in SSPC research through the use of advanced technologies (e.g., single-cell RNA sequencing) allowed discovery of new SSPCs in aging and other conditions, although more investigation is still needed. Understanding these regulatory differences can open new avenues for the discovery of novel treatment approaches for calvarial or long bone repair.