Postnatal Root Dentin Formation: An Emerging Signaling Pathway

Objective: Although differences have been reported between crown and root dentinogenesis, the molecular mechanisms controlling the specificity of these two different processes are largely unknown. The goal of this study is to identify the signaling molecules that control root dentinogenesis.

Method:

1) Bmpr1a (Bmp Receptor 1A) ^fl/fl mice were conditionally knocked out (cKO) by crossing to the 3.2 kb Col 1^ERt2-Cre mice (induced by Tamoxifen injections); 2) Bmpr1a ^fl/fl, 3.2 kb Col 1^ERt2-Cre, and the 3.6 kb Col 1-Osx (a newly produced transgenic mice for overexpressing osterix in pulp/odontoblasts) were crossed for testing if the targeted overexpression of Osx was able to rescue Bmpr1a cKO root phenotype;  3) Combined approaches of histology, SEM, micro-CT, x-ray, and immunohistochemistry were used to characterize the root dentin phenotype in Bmpr1a cKO and the Osx rescued Bmpr1a cKO mice; and 4) Real-time RT-PCR was used to measure changes of genes critical for odontoblast formation in Bmpr1a cKO and the rescued  Bmpr1a cKO (by infection with Adv-CMV-OSX) in vitro.

Result: :  Deletion of Bmpr1a by 3.2 kb Col 1^ERt2-Cre between newborn and 1-month leads to an astonishing root dentin phenotype, including extremely thin dentin, short tooth roots in both the incisors and the molars, enlarged pulp chambers/root canal regions, and malformed dentinal tubules with a greater than 50% reduction of dentin formation rate plus a loss of Osx expression in root odontoblasts, as well as ectopic bone formed within root pulp.  The targeted re-expression of Osx partially rescued the above dentin phenotype. Adv-CMV-OSX infection in Bmpr1a cKO partially reversed expression changes of nestin, OCN and OPN in cKO pulp cells. 

Conclusion: We identified BMPR1A-OSX signaling pathway in root dentinogenesis, which  plays a distinct role in root dentinogenesis.