Extracellular matrix-mediated tissue remodeling following axial movement of teeth.

Tooth eruption is a multifactorial process involving movement of existing tissues and formation of new tissues coordinated by a complex set of genetic events. We have used the model of the unopposed rodent molar to study morphological and genetic mechanisms involved in axial movement of teeth. Following extraction of opposing upper molars, lower molars supererupted by 0.13 mm. Labeled tissue sections revealed significant amounts of new bone and cementum apposition at the root apex of the unopposed side following supereruption for 12 days. Newly apposited cementum and alveolar bone layers were approximately 3-fold thicker in the experimental vs the control group, whereas periodontal ligament width was maintained. Tartrate-resistant acid phosphatase staining indicated bone resorption at the mesial alveolar walls of unopposed molars and provided in tandem with new bone formation at the distal alveolar walls an explanation for the distal drift of molars in this model. Microarray analysis and semiquantitative RT-PCR demonstrated a significant increase in collagen I, integrin beta5, and SPARC gene expression as revealed by comparison between the unopposed molar group and the control group. Immunohistochemical verification revealed increased levels of integrin beta5 and SPARC labeling in the periodontal ligament of the unopposed molar. Together our findings suggest that posteruptive axial movement of teeth was accomplished by significant formation of new root cementum and alveolar bone at the root apex in tandem with upregulation of collagen I, integrin beta5, and SPARC gene expression.

Bones, teeth, and genes: a genomic homage to Harry Sicher's "Axial Movement of Teeth".

AIM: The model of the unopposed rodent molar was used to study the morphologic and genetic mechanisms of tooth eruption. METHODS: Left maxillary molar teeth of 12-day-old Swiss-Webster mice were extracted under anesthesia, and mandibular molars were allowed to supererupt. To trace areas of tissue remodeling and to determine areas of new tissue formation, mice were injected with fluorescent dyes, tetracycline, alizarin red, and calcein blue. Subsequent to sacrifice, mandibular tissue blocks were prepared for ultrathin ground sections, fluorescent microscopy, and von Kossa's mineral detection procedure. A second set of specimens was prepared for RNA extraction and microarray analysis. RESULTS: The data established significant eruption of first and second mandibular mouse molars 12 days after complete extraction of antagonists, exceeding the control side by 0.13 mm. Labeled tissue sections revealed significant amounts of new bone and cementum apposition on the unopposed side compared to the control side, as revealed by fluorescent markers and ultrathin ground sections. Microarray transcript level comparisons between the experimental and the control groups demonstrated significant (more than twofold) increase in gene expression of elastin and tenascin C extracellular matrix proteins; brevican, lumican, and biglycan proteoglycans; as well as fibroblast growth factor 9. CONCLUSION: In this study, the authors have established the unopposed mouse molar as a model to study tissue dynamics during the axial movement of teeth. The data indicated significant new formation of bone and cementum in tandem with increased expression of extracellular matrix-related genes.