Phosphorylated Extracellular Matrix Proteins of Bone and Dentin is the second volume of the e-book series Frontiers between Science and Clinic in Odontology. The phosphorylated proteins of the extracellular matrix of bone and teeth play a crucial structural role in the two tissues. They also act as signaling molecules. Phosphorylated extracellular matrix proteins have been implicated in nucleation and mineralization of skeletal tissues. This e-book covers research on these specific proteins, including details about the cells producing these molecules, their impact on bone and teeth pathology (osteogenesis and dentinogenesis imperfecta) and the potential of these molecules in promoting of inhibiting mineralization. This e-book also explains processes under the control of some enzymes - TNAP and metalloproteases (MMPs) - such as intracellular regulation in bone and dentine, splicing, respective roles of cleavage products, SIBLINGs, nucleation and crystal growth and regulation. This second volume serves as a valuable reference to practicing odontologists, biology and biomaterials scientists and tissue engineers interested in protein research related to tooth and bone formation.

This book addresses the structural and biological properties of dental and peridental tissue structures and covers their mineralization process. The book contains a description of dentines, cementum, enamel and bone, including collagens, as well as non-collagenous proteins (SIBLINGs, SLRPs, GAGs, PGs, lipids, and MMPs). The mechanisms of mineralization are described in detail and the book is focused on matrix vesicles, collagen mineralization and the role of non-collagenous extracellular matrix components either as promoters or inhibitors of mineralization. In addition, the matrix components (non-collagenous) of enamel (amelogenin, ameloblastin, enamelin, MMP4, MMP20 and other proteases) are reviewed and their respective roles in dental tissues biomineralizations and tissue turnover are discussed. Additionally, environmental factors involved in enamel / dentin defects are adressed. With state-of-the-art contributions from experts in the respective domains, the book is a useful introduction to the field for junior scientists, interested in dental and peridental tissue biomineralization. It is also an interesting read for advanced scientists and clinicians working in dental research, giving them a broader view of the topic beyond their area of specialization. The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology.

Mimicking the Extracellular Matrix approaches this topic from both basic science and practical engineering perspectives. Suitable for undergraduates, postgraduates, and academics, this text aims to unify the current knowledge of ECM biology and matrix-mimicking biomaterials.

Dentin matrix protein 1 (DMP1) is a highly phosphorylated extracellular matrix protein, predominantly expressed in osteocytes in bone. Full-length DMP1 is enzymatically processed into a 37 kDa N- and a 57 kDa C-terminal fragment in vivo. The goal of this study was to identify the cis-regulatory regions that control osteoctye-specific expression of the DMP1 gene, to determine the in vivo function of the 57 kDa C-terminal fragment and to determine the role of DMP1 in control of phosphate homeostasis.

The proliferation and differentiation of osteoblasts are influenced by mechanical and geometrical growth environments. A specific aim of my thesis was the elucidation of signaling pathways involved in mechanical stimulation and geometric alterations of the extracellular matrix (ECM). A pair of questions addressed herein was (a) Does mechanical stimulation modulate translational regulation through the phosphorylation of eukaryotic initiation factor 2a (eIF2a)? (b) Do geometric alterations affect the phosphorylation patterns of mitogen-activated protein kinase (MAPK) signaling? My hypothesis was mechanical stress enhances the proliferation and survival of osteoblasts through the reduction in phosphorylation of eIF2a, while 3-dimensional (3D) ECM stimulates differentiation of osteoblasts through the elevation of phosphorylation of p38 MAPK. First, mechanical stimulation reduced the phosphorylation of eIF2a. Furthermore, flow pre-treatment reduced thapsigargin-induced cell mortality through suppression of phosphorylation of protein kinase RNA-like ER kinase (Perk). However, H2O2-driven cell mortality, which is not mediated by Perk, was not suppressed by mechanical stimulation. Second, in the ECM geometry study, the expression of the active (phosphorylated) form of p130Cas, focal adhesion kinase (FAK) and extracellular signal-regulated protein kinase (ERK) was reduced in cells grown in the 3D matrix. Conversely, phosphorylation of p38 MAPK was elevated in the 3D matrix and its up-regulation was linked to an increase in mRNA levels of dentin matrix protein 1 and bone sialoprotein. In summary, our observations suggest the pro-survival role of mechanical stimulation and the modulation of osteoblastic fates by ECM geometry.