Bmp2 Deletion Causes an Amelogenesis Imperfecta Phenotype Via Regulating Enamel Gene Expression

Abstract

Although Bmp2 is essential for tooth formation, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in regulation of enamel formation was investigated by the Bmp2 conditional knock out (Bmp2 cKO) mice. Teeth of Bmp2 cKO mice displayed severe and profound phenotypes with asymmetric and misshaped incisors as well as abrasion of incisors and molars. Scanning electron microscopy analysis showed that the enamel layer was hypoplastic and enamel lacked a typical prismatic pattern. Teeth from null mice were much more brittle as tested by shear and compressive moduli. Expression of enamel matrix protein genes, amelogenin, enamelin, and enamel-processing proteases, Mmp-20 and Klk4 was reduced in the Bmp2 cKO teeth as reflected in a reduced enamel formation. Exogenous Bmp2 up-regulated those gene expressions in mouse enamel organ epithelial cells. This result for the first time indicates Bmp2 signaling is essential for proper enamel development and mineralization in vivo.

Establishment of Immortalized Mouse Bmp2 Knock‐Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis

“…In Bmp2 cKO mice, bone fracture healing was impaired (Tsuji et al, ) and teeth exhibited small sizes compared to that of the wild type (normal and Bmp2 fx/fx ) mice (Feng et al, ; Guo et al, ). We noted that the iBmp2 ko/ko dp cell growth is slow compared to that of the iBmp2 fx/fx dp cells.…”

“…Also, Bmp2 promotes dental pulp stem cell commitment to odontoblast lineages (Yang et al, ) and induces dental pulp cell differentiation (Chen et al, ; Cho et al, ). Bmp2 conditional knock‐out (cKO) mice display abnormal tooth phenotypes with delayed odontoblast differentiation, abnormal dentin tubules, and decrease tooth‐related gene expression (Feng et al, ; Yang et al, ; Guo et al, ).…”

“…Bmp2 expression is observed in dental cells during tooth development (Aberg et al, 1997). Also, Bmp2 promotes dental pulp stem cell commitment to odontoblast lineages (Yang et al, 2009) and differentiation, abnormal dentin tubules, and decrease tooth-related gene expression (Feng et al, 2011;Yang et al, 2012;Guo et al, 2014). However, roles of Bmp2 during odontogenesis have not been completely understood.…”

Common mechanisms in development and disease: BMP signaling in craniofacial development

“…Loss of Follistatin, a Bmp and Activin antagonist expressed in enamel-free lingual dental epithelium, resulted in ectopic enamel deposition, whereas it's overexpression inhibited ameloblast differentiation [74]. Deletion of Bmp2 in odontoblasts (Osx-Cre) led to deregulated expression of Amel and Enam , two enamel matrix proteins, and Klk4 and Mmp20 , two enamel processing proteases [75]. In humans, mutations in MMP20, KLK4 and ENAM are associated with Amelogenesis Imperfecta (AI) [76-81].…”

“…size and shape of mandible, nasal bone, skull bones), but do not investigate if these changes also affect the quality of the mineralized or non-mineralized structures. Bmp signaling controls tooth mineralization [75, 83], bone formation and homeostasis (reviewed in [132-134]). Thus, it is possible to speculate that BMP signaling may regulate quality of minerals such as crystallinity and mineral matrix ratio (MMR).…”