Disrupted Alveolar Bone, Calvaria, and Teeth with Altered Glucocorticoid Signaling

Glucocorticoid excess leads to a decrease in bone mass. We previously showed that disruption of glucocorticoid signaling in mice with an 11ß-hydroxysteroid dehydrogenase transgene (Col2.3-HSD2) targeted to mature osteoblasts led to lower vertebral bone mass and decreased osteoblast differentiation ex vivo.

Objectives: To assess the role of endogenous glucocorticoids in the craniofacial complex, we examined the effects of reduced glucocorticoid signaling in calvaria, alveolar bone, and incisors of transgenic mice in which the 11ß-HSD2 transgene was expressed broadly in the osteoblasts and odontoblasts (Col3.6-HSD2).

Methods: Transgene mRNA expression was assessed by Northern blot analysis in neonatal calvaria. Transgene protein was evaluated by immunohistochemistry with a rat 11ß-HSD2 antibody in mandibles of 6-week-old mice. The morphometry of calvaria, mandibular alveolar bone, and teeth was assessed in 6-week-old mice using X-ray microcomputed tomography.

Results: Transgene mRNA was expressed highly in calvaria. Transgene protein was localized to osteoblasts and odontoblasts in alveolar bone and teeth, respectively. The calvaria from transgenic (TG) mice were smaller and thinner compared to wild type (WT) calvaria in both males (n=6WT, 6TG) and females (n=7WT, 5TG). In females, the amount of marrow space in transgenic calvariae was significantly increased (WT=6.4±1%; TG=15.2%±2%**) leading to decreased bone volume (WT=93.6±1%; TG=84.8±2%**). Alveolar bone volume tended to be lower in transgenic females (WT=71.2±2%; TG=70.5±2%) and males (WT=72.7±1%; TG=68.2±1%**). Incisors from transgenic mice were smaller, seen as decreased cross-sectional area in females (WT=0.46±0.02mm2; TG=0.41±0.02mm2*) and males (WT=0.48±0.01mm2; TG=0.43±0.01mm2**). The pulp chambers were smaller in female transgenic incisors (WT=0.129±0.014mm2, TG=0.080±0.007mm2*). In addition, transgenic incisors showed decreased surface area and mineral density corresponding to dentin and increased surface area and mineral density corresponding to enamel. (*p<0.05,**p<0.01).

Conclusion: These data indicate that endogenous glucocorticoids are necessary for optimal acquisition of craniofacial bone mass, normal dentin morphology and appropriate enamel initiation.

NIAMS AR048602