Osteoinductivity of calcium phosphate mediated by connexin 43

Recent reports have alluded to the osteoinductive properties of calcium phosphate, yet the cellular processes behind this are not well understood. To gain insight into the molecular mechanisms of this phenomenon, we have conducted a series of in vitro and in vivo experiments using a scaffoldless three dimensional (3D) dental pulp cell (DPC) construct as a physiologically relevant model. We demonstrate that amorphous calcium phosphate (ACP) alters cellular functions and 3D spatial tissue differentiation patterns by increasing local calcium concentration, which modulates connexin 43 (Cx43)-mediated gap junctions. These observations indicate a chemical mechanism for osteoinductivity of calcium phosphates. These results provide new insights for possible roles of mineral phases in bone formation and remodeling. This study also emphasizes the strong effect of scaffold materials on cellular functions and is expected to advance the design of future tissue engineering materials.