Biomolecular Cell-Signaling Mechanisms and Dental Implants: A Review on the Regulatory Molecular Biologic Patterns Under Functional and Immediate Loading

Purpose: Bone tissue adapts its structure and mass to the stresses of mechanical loading. The purpose of this review article was to summarize recent advances on cell signaling relating to the phenomenon of bone remodeling, focused on bone ossification and healing at the interface of dental implants and bone under loading conditions. Materials and Methods: When a dental implant is placed within an osteotomy, osteocytes, osteoblasts, and osteoclasts are all present. As functional loads are imposed, the remodeling processes adapt the peri-implant bony tissues to mechanical stimuli over time and reestablish a steady state. Based on the current literature, this article demonstrates fundamental information to these remodeling processes, such as the conversion of mechanical cues to electrical or biochemical signals. Results: Multiple intracellular signals are involved in cellular mechanotransduction; the two Wnt signaling pathways (the canonical, β-catenin-dependent and the noncanonical, β-catenin-independent Wnt pathway) are particularly significant. Knowledge of how these molecular signaling pathways are translated into intracellular signals that regulate cell behavior may provide new therapeutic approaches to enhancing osteogenesis, especially around implants with immediate function or placed in areas of poor bone quality. New knowledge about the primary cilia as an organelle and bone cellular mechanosensor is critical for endochondral ossification and proper signal transduction. Other mechanisms, such as the expression of sclerostin as a negative regulator of bone formation (due to deactivation of the Wnt receptor) and downregulation of sclerostin under loading conditions, also present new understanding of the cellular and pericellular mechanics of bone. Conclusion: The complexity of the cell signaling pathways and the mechanisms involved in the mechanoregulation of the bone formation provide new technologies and perspectives for mechanically induced cellular response. Future novel therapeutic approaches based on the cell signaling pathways may improve and stimulate osseointegration of dental implants and accelerate the healing mechanisms. Keywords: β-catenin, cell signaling, molecular biology, Wnt signaling