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1. A computerized model for reconstruction of dental ontogeny: A new tool for studying evolutionary trends in the dentition.

Author

Delson, Eric, MacPhee, Ross D.E., Conard, Nicholas, Fleagle, John G., McBrearty, Sally, Meng, Jin, Plummer, Tom, Rogers, Kristi Curry, Rose, Ken, Bailey, Shara E., Hublin, Jean-Jacques, Smith, P., Müller, R., Gabet, Y., and Avishai, G.

Abstract

All hominid molars show the same sequence of cusp initiation, but differ in the later stages of development. The topography of the dentin-enamel junction (DEJ) represents the outcome of differential growth between cusps. Since the cusps grow in an orderly sequence from tip to base (defined by the plane of coalescence with adjacent cusps), quantification of cusp volume and relationships can be used to reconstruct successive stages in development and their contribution to the morphometry of the crown surface. Their volume and spatial relationships at the DEJ enable us to partition cell proliferation in relation to cusp initiation, while quantification of the amount and distrib ution of enamel overlying the DEJ provides the necessary discrimination between cell proliferation and cell function, expressed in enamel matrix apposition. We have developed a three-dimensional computerized model of a lower molar tooth that enables us to identify and quantify the different stages of tooth development defined above. The model is based on serial micro-computed tomography (microCT) images of human teeth that provide accurate quantification of the outer and inner enamel and dentin boundaries of individual cusps. We have used this model to compare morphogenesis in the lower second deciduous molar and lower first permanent molar. Spatial relationships of the cusps, expressed by the topography of the DEJ showed that shape differences were established in the early stages of morphogenesis by differential proliferation within the developing tooth germ and that cusp size and proportions were modified at the crown surface by enamel apposition. Reduction of the hypoconulid in the permanent molar shown at the DEJ was largely masked by the exceptional thickness of enamel on this cusp. We propose that this model provides a novel contribution to the identification of ontogenetic trajectories and their contribution to evolutionary trends in tooth size, shape and enamel thickness. [ABSTRACT FROM AUTHOR]

Published
2007
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2. Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells.

Author

Baniwal, S., Shah, P., Shi, Y., Haduong, J., DeClerck, Y., Gabet, Y., and Frenkel, B.

Subjects
BONE physiology, GENE expression, POLYMERASE chain reaction, RESEARCH funding, T-test (Statistics), WESTERN immunoblotting, EQUIPMENT & supplies, REVERSE transcriptase polymerase chain reaction, MICROARRAY technology
Abstract

Summary: We profiled the global gene expression of a bone marrow-derived mesenchymal pluripotent cell line in response to Runx2 expression. Besides osteoblast differentiation, Runx2 promoted the osteoclastogenesis of co-cultured splenocytes. This was attributable to the upregulation of many novel osteoclastogenic genes and the downregulation of anti-osteoclastogenic genes. Introduction: In addition to being a master regulator for osteoblast differentiation, Runx2 controls osteoblast-driven osteoclastogenesis. Previous studies profiling gene expression during osteoblast differentiation had limited focus on Runx2 or paid little attention to its role in mediating osteoblast-driven osteoclastogenesis. Methods: ST2/Rx2, a bone marrow-derived mesenchymal pluripotent cell line that expresses Runx2 in response to Doxycycline (Dox), was used to profile Runx2-induced gene expression changes. Runx2-induced osteoblast differentiation was assessed based on alkaline phosphatase staining and expression of classical marker genes. Osteoclastogenic potential was evaluated by TRAP staining of osteoclasts that differentiated from primary murine splenocytes co-cultured with the ST2/Rx2 cells. The BeadChip™ platform (Illumina) was used to interrogate genome-wide expression changes in ST2/Rx2 cultures after treatment with Dox or vehicle for 24 or 48 h. Expression of selected genes was also measured by RT-qPCR. Results: Dox-mediated Runx2 induction in ST2 cells stimulated their own differentiation along the osteoblast lineage and the differentiation of co-cultured splenocytes into osteoclasts. The latter was attributable to the stimulation of osteoclastogenic genes such as Sema7a, Ltc4s, Efnb1, Apcdd1, and Tnc as well as the inhibition of anti-osteoclastogenic genes such as Tnfrsf11b (OPG), Sema3a, Slco2b1, Ogn, Clec2d (Ocil), Il1rn, and Rspo2. Conclusion: Direct control of osteoblast differentiation and concomitant indirect control of osteoclast differentiation, both through the activity of Runx2 in pre-osteoblasts, constitute a novel mechanism of coordination with a potential crucial role in coupling bone formation and resorption. [ABSTRACT FROM AUTHOR]

Published
2012
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