Periosteal Skeletal Stem Cells and Their Response to Bone Injury

Abstract

Bone exhibits remarkable self-repair ability without fibrous scars. It is believed that the robust regenerative capacity comes from tissue-resident stem cells, such as skeletal stem cells (SSCs). Roughly, SSC has two niches: bone marrow (BM) and periosteum. BM-SSCs have been extensively studied for years. In contrast, our knowledge about periosteal SSCs (P-SSCs) is quite limited. There is abundant clinical evidence for the presence of stem cell populations within the periosteum. Researchers have even successfully cultured "stem-like" cells from the periosteum in vitro. However, due to the lack of effective markers, it is difficult to evaluate the stemness of real P-SSCs in vivo. Recently, several research teams have developed strategies for the successful identification of P-SSCs. For the first time, we can assess the stemness of P-SSCs from visual evidence. BM-SSCs and P-SSCs not only have much in common but also share distinct properties. Here, we provide an updated review of P-SSCs and their particular responses to bone injury.

Keywords: bone repair; fate decision; lineage tracing; periosteum; skeletal stem cell.

FIGURE 1

The development of P-SSCs and their differentiation capacity. (A) In the limb development, a cartilage template is first established; the perichondrium contains undifferentiated mesenchymal cells. (B) Ossification begins when the blood vessel invades the center of the cartilage; the perichondrium is changed into periosteum. The perichondral mesenchymal cells give rise to P-SSCs. (C) Skeletal stem cells (SSCs) in different sites of the femur have distinct differentiation abilities. Compared with bone marrow-SSCs (BM-SSCs) and growth plate-SSCs (GP-SSCs) the periosteal SSCs (P-SSCs) can only give rise to osteoblasts at baseline.

FIGURE 2

The response of P-SSCs in different bone injury models. (A) In unstable fracture condition, P-SSCs acquire the capacity to differentiate into chondrocytes. (B) In DO or defected condition, P-SSCs showed high migratory capabilities. They are recruited into the bone defect site in response to special migration signals.