1. The Role of EMC+ Mesenchymal Stromal Cells and
EP4 Signaling in Bone Maintenance and Regeneration
Mary Lin, Christine Eisner, Fabio Rossi
Biomedical Research Centre
University of British Columbia, Vancouver, BC V6T 1Z4, CANADA
Bone is one of the few adult tissues capable of complete regeneration throughout life and following injury.
This ability of regeneration is in part due to the contributions of bone maintenance cells known as osteoclasts
and osteoblasts which reabsorb and deposit bone, respectively. While the hematopoietic origins of osteoclasts
are well documented, the identity of mesenchymal progenitors that give rise to bone-lining osteoblasts is not
well understood. Previously, various populations of multipotent mesenchymal progenitors prevalent in muscle,
bone, and other adult tissues have been identified. One subpopulation of these mesenchymal progenitors
includes EMC+ cells, whose precise role in bone maintenance and regeneration has not yet been described.
This study also evaluates the EP4 signaling pathway and the effects of deleting the EP4 receptor from cells
involved with bone regeneration. Previous research has indicated that the EP4 receptor has the ability to
regulate and induce bone formation. To track the response of EMC+ cells to bone injury, an inducible CreERT2
reporter strain of mice was used. It was discovered that EMC+ cells from the periosteal region of the bone are
involved in the formation of the callus after bone injury, a critical stage in bone regeneration. Using the same
inducible EMC-CreERT2, a different strain of mice was generated, in which the EP4 receptor was removed
from EMC-expressing cells. Through histology, cell differentiation assays, and gene expression analysis, the
effects of EP4 deletion on bone homeostasis and bone regeneration can be analyzed. The results from this study
may contribute to improving drug treatments from patients suffering from metabolic bone diseases including
osteoporosis and osteogenesis imperfecta.