Abstract
Dental Mesenchymal Cells (DMCs) are known to play a role in tooth development as well as in the repair and regeneration of dental tissue. A large number of signaling molecules regulate the proliferation and differentiation of DMC, though the underlying mechanisms are still not fully understood. Sirtuin-6 (SIRT6), a key regulator of aging, can exert an impact on embryonic stem cell (ESC) differentiation. The experimental deletion of Sirt6 in mouse bone marrow cells has been found to have an inhibiting impact on the bone mineral density and the osteogenic differentiation of these cells. The possible role of Sirt6 in tooth development, however, has at present remained largely unexplored. In the present study, we found that SIRT6 had no effect on tooth development before birth. However, Sirt6 gene deletion in knockout mice did have two post-natal impacts: a delay in tooth eruption and sluggishness in the development of dental roots. We propose an explanation of the possible molecular basis of the changes observed in Sirt6-/- mice. SIRT6 is expressed in mouse odontoblasts. Sirt6 deletion enhanced the proliferation of DMCs, as well as their capacity for adipogenic differentiation. On the other hand, it inhibited their capacity for in vitro osteogenic/chondrogenic differentiation. Further studies suggested that other factors may mediate the role of Sirt6 in odontogenesis. These include the nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (p38-MAPK), extracellular regulated MAP kinase (ERK) pathways and the mitochondrial energy. We demonstrated that Sirt6 plays a role in tooth root formation and confirmed that SIRT6 is necessary for DMC differentiation as well as for the development of the tooth root and for eventual tooth eruption. These results establish a new link between SIRT6 and tooth development.
Highlights
Tooth development is a long, complex biological process that includes epithelial and mesenchymal interactions, cell differentiation, morphogenesis, tissue mineralization, and tooth eruption
Our findings reveal that there may be an additional mechanism governing the process of tooth development: the protein-coding Sirt6 gene
Our work has established that SIRT6 is expressed in mouse odontoblasts and is capable of regulating the proliferation and differentiation of Dental Mesenchymal Cells (DMCs), SIRT6’s contribution to the process of tooth development appears to occur via interaction with the p38-mitogen-activated protein kinase (MAPK), extracellular regulated MAP kinase (ERK), and NF-κB signal pathways and with the process of mitochondrial energy metabolism
Summary
Tooth development is a long, complex biological process that includes epithelial and mesenchymal interactions, cell differentiation, morphogenesis, tissue mineralization, and tooth eruption. Numerous studies have reported the roles of Dental Mesenchymal Cells (DMCs) in tooth development. Several types of DMCs have already been identified from different sources. Among these sources are dental pulp, periodontal ligament, exfoliated deciduous teeth, dental follicle (DF), root apical papilla, human periapical cysts and dental bud [4,5,6,7,8,9,10,11]. Similar to embryonic stem cells, the proliferation and differentiation of DMCs is associated with biological molecules. The interplay between DMCs and these molecules remains largely unknown
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