Bone is often viewed as the most promising target tissue in the field of regenerative medicine, and various strategies have been developed to differentiate bone-forming osteoblasts, both in vitro and in vivo. However, the molecular and cellular mechanisms of "bone remodeling" and "endochondral ossification (intracartilaginous ossification)" are not completely understood. Bone remodeling is a sequential process in which osteoclastic bone resorption is followed by osteoblastic bone formation, and this process is usually considered to maintain the bone size and shape. In contrast, endochondral ossification is a process to replace a cartilaginous template with bone. Endochondral ossification occurs both in the process of bone development and repair. All these processes are controlled by cell-cell interactions. In this project, we propose to analyze the interactions among bone cells, such as osteoclasts, osteoblasts, osteocytes and chondrocytes. Possible interactions with vascular endothelial cells and neurons will also be considered. First, we shall analyze roles of ephrinA ligands and EphA receptors in bone remodeling. By using bone fracture healing models in mice, we shall also analyze cross-talks between inflammatory cells and chondrocyte progenitors during endochondral ossification. How osteoblasts establish cell polarity to form bone during the process of endochondral ossification will be another focus of this project.