Manipulation of signaling pathways in bone tissue engineering and regenerative medicine: Current knowledge, novel strategies, and future directions.

During osteogenesis, a large number of bioactive molecules, macromolecules, cells, and cellular signals are activated to induce bone growth and development. The activation of molecular pathways leads to the occurrence of cellular events, ultimately resulting in observable changes. Therefore, in the studies of bone tissue engineering and regenerative medicine, it is essential to target fundamental events to exploit the mechanisms involved in osteogenesis. In this context, signaling pathways are activated during osteogenesis and trigger the activation of numerous other processes involved in osteogenesis. Direct influence of signaling pathways should allow to manipulate the signaling pathways themselves and impact osteogenesis. A combination of sequential cascades takes place to drive the progression of osteogenesis. Also, the occurrence of these processes and, more generally, cellular and molecular processes related to osteogenesis necessitate the presence of transcription factors and their activity. The present review focuses on outlining several signaling pathways and transcription factors influencing the development of osteogenesis, and describes various methods of their manipulation to induce and enhance bone formation.