1) Bmpr1a (Bmp Receptor 1A) fl/fl mice were conditionally knocked out (cKO) by crossing to the 3.2 kb Col 1ERt2-Cre mice (induced by Tamoxifen injections); 2) Bmpr1a fl/fl, 3.2 kb Col 1ERt2-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 1ERt2-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.
Keywords: Cell biology, Dentin, Odontoblasts, Pulp and Root
See more of: Pulp Biology & Regeneration Research