ABSTRACT
NELL-1 is a potent osteoinductive molecule that enhances bone formation in multiple animal models through currently unidentified pathways. In the present manuscript, we hypothesized that NELL-1 may regulate osteogenic differentiation accompanied by alteration of inorganic phosphate (Pi) entry into the osteoblast via sodium dependent phosphate (NaPi) transporters. To determine this, MC3T3-E1 pre-osteoblasts were cultured in the presence of recombinant human (rh)NELL-1 or rhBMP-2. Analysis was performed for intracellular Pi levels through malachite green staining, Pit-1 and Pit-2 expression, and forced upregulation of Pit-1 and Pit-2. Results showed rhNELL-1 to increase MC3T3-E1 matrix mineralization and Pi influx associated with activation of both Pit-1 and Pit-2 channels, with significantly increased Pit-2 production. In contrast, Pi transport elicited by rhBMP-2 showed to be associated with increased Pit-1 production only. Next, neutralizing antibodies against Pit-1 and Pit-2 completely abrogated the Pi influx effect of rhNELL-1, suggesting rhNELL-1 is dependent on both transporters. These results identify one potential mechanism of action for rhNELL-1 induced osteogenesis and highlight a fundamental difference between NELL-1 and BMP-2 signaling.
Subject(s)
Calcification, Physiologic/physiology , Nerve Tissue Proteins/metabolism , Osteoblasts/physiology , Osteogenesis/physiology , Sodium-Phosphate Cotransporter Proteins, Type III/metabolism , Alkaline Phosphatase/metabolism , Animals , Bone Morphogenetic Protein 2/metabolism , Calcification, Physiologic/drug effects , Calcium-Binding Proteins , Cell Line , Extracellular Matrix/metabolism , Extracellular Matrix/physiology , Humans , Mice , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/pharmacology , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Signal TransductionABSTRACT
INTRODUCTION: The aims of this study were to develop a method for constructing a 3-dimensional finite-element model (FEM) of the maxilla and to evaluate the effects of transverse expansion on the status of various midpalatal sutures. METHODS: A 3-dimensional FEM of the craniofacial complex was developed by using computed-tomography images and Bionix modeling software (version 3.0, CANTIBio, Suwon, Korea). To evaluate the differences between transverse expansion forces in the solid model (maxilla without a midpalatal suture), the fused model (maxilla with suture elements), and the patent model (maxilla without suture elements), transverse expansion forces of 100 g were applied bilaterally to the maxillary first premolars and the first molars. RESULTS: The fused model expressed a stress pattern similar to that of the solid model, except for the decreased first principal stress concentration in the incisive foramen area. The patent model, however, had a unique stress pattern, with the stress translated superiorly to the nasal area. The anterior nasal spine and the central incisors moved downward and backward in both solid and fused models but moved primarily downward with a slight backward movement of the anterior nasal spine in the patent model. CONCLUSIONS: Clinical observations of maxillary expansion can be explained by different suture statuses. This efficient and customized FEM model can be used to predict craniofacial responses to biomechanics in patients.
