Bone Morphogenetic Proteins 7 Induces Tooth Mineralization

Objectives: Dental enamel is the hardest and most mineralized tissue in the vertebrate species. The polarized cells of the enamel organ known as ameloblast cells lay down the protein matrix for ordered enamel crystal growth. Prior to onset of tooth mineralization there is a molecular cross talk between dental epithelium and dental mesenchyme that controls differentiation into ameloblasts and odontoblasts, respectively. Various Bone Morphogenetic Proteins are expressed in early differentiating ameloblasts and odontoblasts just prior to the onset of tooth mineralization. We had recently shown that BMP2 coordinates tooth mineralization. Here we investiged the role BMP7 in tooth mineralization.
Methods: BMP7 expression was determined using Bmp7LacZ reporter mice. Bmp7 was deleted in neural crest cells, which includes the dental mesenchyme using Wnt1-Cre (Bmp7^ncko). Histology and immunohistochemistry was performed on paraffin section of 1^st upper molars. Mineralization was assessed using microCT and back scatter SEM.
Results: Bmp7 expression in odontoblasts was restricted to tooth cusps of the developing molars, where mineralization is initiated. Bmp7^ncko molars showed a complete block of dentin and enamel differentiation at birth, the time when mineralization of the upper molars is initiated. Loss of Bmp7 did not alter pSmad1/5/8 activity, however, it had a profound effect on Wnt signaling with a strongly reduction of non-phosphorylated, active signaling b-catenin in pre-ameloblasts. Tooth mineralization was initiated 48-72 hours later and enamel volume was still reduced at P4 and P8. Enamel quality as well as cusp shape was altered in adult teeth. Molars were short, broad, with alterations in cusp orientation, morphology, and attrition facets. The enamel showed structural changes indicative of reduced mineral density and/or quality.
Conclusions: BMP7 acts independent of BMP2. It induces tooth mineralization and its adoption could have improved enamel quality in addition to contributing to dental diversity.