The periosteum supplies osteoblasts and nutrients for bone metabolism and is important for osteoblast differentiation and osteogenesis. Recently, periosteum-derived cells have been used for orofacial bone regeneration therapy. However, little is known about the function of the periosteum in physiological bone remodeling. On our hypothesis that the periosteum senses a mechanical stress to induce bone remodeling, we subjected human jaw bone periosteum cells (HJBPCs) to uniaxial stretching for 24 h and characterized their gene expression profiles by microarray analysis. Of62,976 genes detected, 550 genes related to bone metabolism were extracted, and 76 of these genes with large changes in gene expression were short-listed. The results indicated that mechanical stretch in HJBPCs regulated the expression levels of genes involved in the Wingless-type MMTV integration (Wnt) site, bone morphogenetic protein (BMP) signaling pathways, and inflammatory cytokines. We propose that periosteum-derived cells sense mechanical stress and then activate and regulate signals for osteoblast differentiation and osteogenesis.