Substrate stiffness promotes dentinogenesis via LAMB1–FAK–MEK1/2 signaling axis.

Objectives: In vivo, the principal function of mechanosensitive odontoblasts is to synthesize and secrete the matrix which then calcifies and forms reactive dentin after exposure to appropriate stimuli. This study aims to develop the influence of mechanical factors on dentinogenesis based on odontoblasts, which contribute to reparative dentin formation. Methods: We fabricated polydimethylsiloxane with different stiffnesses and seeded 17IIA11 odontoblast‐like cells on the substrates in different stiffnesses. Cell morphology was detected by scanning electron microscope, and the mineralization phenotype was detected by alkaline phosphatase staining and alizarin red staining, while expression levels of dentinogenesis‐related genes (including Runx2, Osx, and Alp) were assayed by qPCR. To explore mechanism, protein distribution and expression levels were detected by immunofluorescent staining, Western blotting, and immunoprecipitation. Results: In our results, during dentinogenesis, 17IIA11 odontoblast‐like cells appeared better extension on stiffer substrates. The binding between LAMB1 and FAK contributed to converting mechanical stimuli into biochemical signaling, thereby controlling mitogen‐activated protein kinase kinase 1/2 activity in stiffness‐driven dentinogenesis. Conclusion: The present study suggests odontoblast behaviors can be directly regulated by mechanical factors at cell–material interfaces, which offers fundamental mechanism in remodeling cell microenvironment, thereby contributing to physiological phenomena explanation and tissue engineering progress. [ABSTRACT FROM AUTHOR]