This study examines the role of EMC+ mesenchymal stromal cells and EP4 signaling in bone maintenance and regeneration. It was discovered that EMC+ cells from the periosteal region are involved in forming the callus after bone injury, an important stage in regeneration. The study also evaluates the effects of deleting the EP4 receptor from EMC-expressing cells involved in regeneration. By analyzing histology, cell differentiation, and gene expression with mice lacking the EP4 receptor, the impacts on bone homeostasis and regeneration can be determined. The results may help improve drug treatments for metabolic bone diseases like osteoporosis.