DMP1 Binds Specifically to Type I Collagen and Regulates Mineral Nucleation and Growth

The I-TASSER algorithm for 3D protein structure prediction was tested in CASP8, with the procedure fully automated in both the Server and Human sections. The quality of the server models is close to that of human ones but the human predictions incorporate more diverse templates from other servers which improve the human predictions in some of the distant homology targets. For the first time, the sequence-based contact predictions from machine learning techniques are found helpful for both template-based modeling (TBM) and template-free modeling (FM). In TBM, although the accuracy of the sequence based contact predictions is on average lower than that from template-based ones, the novel contacts in the sequence-based predictions, which are complementary to the threading templates in the weakly or unaligned regions, are important to improve the global and local packing in these regions. Moreover, the newly developed atomic structural refinement algorithm was tested in CASP8 and found to improve the hydrogen-bonding networks and the overall TM-score, which is mainly due to its ability of removing steric clashes so that the models can be generated from cluster centroids. Nevertheless, one of the major issues of the I-TASSER pipeline is the model selection where the best models could not be appropriately recognized when the correct templates are detected only by the minority of the threading algorithms. There are also problems related with domain-splitting and mirror image recognition which mainly influences the performance of I-TASSER modeling in the FM-based structure predictions. Copyright 2009 Wiley-Liss, Inc.

Odontoblasts produce most of the extracellular matrix (ECM) components found in dentin and implicated in dentin mineralization. Major differences in the pulp ECM explain why pulp is normally a non-mineralized tissue. In vitro or in vivo, some dentin ECM molecules act as crystal nucleators and contribute to crystal growth, whereas others are mineralization inhibitors. After treatment of caries lesions of moderate progression, odontoblasts and cells from the sub-odontoblastic Höhl's layer are implicated in the formation of reactionary dentin. Healing of deeper lesions in contact with the pulp results in the formation of reparative dentin by pulp cells. The response to direct pulp-capping with materials such as calcium hydroxide is the formation of a dentinal bridge, resulting from the recruitment and proliferation of undifferentiated cells, which may be either stem cells or dedifferentiated and transdifferentiated mature cells. Once differentiated, the cells synthesize a matrix that undergoes mineralization. Animal models have been used to test the capacity of potentially bioactive molecules to promote pulp repair following their implantation into the pulp. ECM molecules induce either the formation of dentinal bridges or large areas of mineralization in the coronal pulp. They may also stimulate the total closure of the pulp in the root canal. In conclusion, some molecules found in dentin extracellular matrix may have potential in dental therapy as bioactive agents for pulp repair or tissue engineering.

There is substantial practical interest in the mechanism by which the carbonated apatite of bone mineral can be initiated specifically in a matrix. The current literature is replete with studies aimed at mimicking the properties of vertebrate bone, teeth, and other hard tissues by creating organic matrices that can be mineralized in vitro and either functionally substitute for bone on a permanent basis or serve as a temporary structure that can be replaced by normal remodeling processes. A key element in this is mineralization of an implant with the matrix and mineral arranged in the proper orientations and relationships. This review examines the pathway to crystallization from a supersaturated calcium phosphate solution in vitro, focusing on the basic mechanistic questions concerning mineral nucleation and growth. Since bone and dentin mineral forms within collagenous matrices, we consider how the in vitro crystallization mechanisms might or might not be applicable to understanding the in vivo processes of biomineralization in bone and dentin. We propose that the pathway to crystallization from the calcium phosphate-supersaturated tissue fluids involves the formation of a dense liquid phase of first-layer bound-water hydrated calcium and phosphate ions in which the crystallization is nucleated. SIBLING proteins and their in vitro analogs, such as polyaspartic acids, have similar dense liquid first-layer bound-water surfaces which interact with the dense liquid calcium phosphate nucleation clusters and modulate the rate of crystallization within the bone and dentin collagen fibril matrix.