Non-receptor protein kinases FAK and Src play crucial roles in regulating cellular adhesions, growth, migration and differentiation. However, it remains unclear how the activity of FAK and Src is regulated during the differentiation process from mesenchymal stem cells (MSCs) to bone cells. In this study, we used genetically encoded FAK and Src biosensors based on fluorescence resonance energy transfer (FRET) to monitor the FAK and Src activity in live cells during the differentiation process. The results revealed that the FAK activity increased after the induction of differentiation, which peaked around 20–27 days after induction. Meanwhile, the Src activity decreased continuously for 27 days after induction. Therefore, the results showed significant and differential changes of FAK and Src activity upon induction. This opposite trend between FAK and Src activation suggests novel and un-coupled Src/FAK functions during the osteoblastic differentiation process. These results should provide important information for the biochemical signals during the differentiation process of stem cells toward bone cells, which will advance our understanding of bone repair and tissue engineering.

Professor Shu Chien is a world-renowned leader and founder of Bioengineering. In particular, he has made seminal contributions to advancing our systematic and insightful understanding of how cells perceive their physical/mechanical environment and coordinate cellular functions. In this review, as part of a tribute to Prof. Shu Chien's scientific achievement, we summarize the research progress in understanding the physiology of bone cells interacting with different mechanical/physical environments during bone tissue regeneration/repair. We first introduce the cellular composition of the bone tissue and the mechanism of the physiological bone regeneration/repair process. We then describe the properties and development of biomaterials for bone tissue engineering, followed by the highlighting of research progresses on the cellular response to mechanical environmental cues. Finally, several latest advancements in bone tissue regeneration and remaining challenges in the field are discussed for future research directions.

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