One of the major unanswered questions in the calcified tissues field is how and why mineral is deposited at discrete sites, and conversely what normally prevents the unwanted deposition of mineral at other sites. The goal of this investigation continues to be the elucidation of the mechanism of biologic calcification. Specific emphasis will be placed on (1) the factors controlling initial mineral deposition and (2) the factors regulating proliferation and growth of the mineral. The proposed studies will examine cellular factors (membrane lipid composition), hormonal factors (vitamin D), extracellular matrix factors (the non-collagenous proteins: - phosphoproteins, sialoproteins, proteoglycans, proteolipids, and blood-derived proteins), and chemical factors (Ca x P) concentration) which may play a role in controlling initial mineral deposition and/or growth and proliferation of hydroxyapatite crystals. Studies will be based on previously developed lipid-induced calcification, gel growth, seeded growth and in vitro cell mediated calcification systems, as well as analysis of matrix vesicle and animal models. Analytical techniques to be used include: x-ray diffraction and infrared analyses, chemical analyses, and light, scanning and transmission electron microscopy. The ultimate goal of this project is to elucidate the details of the cascade of events involved in physiologic calcification. These details are crucially needed for the development of new and improved therapies for diseases of bones and teeth characterized by impaired, defective, or excessive mineral deposition.
| Villarreal-Ramirez, Eduardo; Eliezer, David; Garduño-Juarez, Ramon et al. (2017) Phosphorylation regulates the secondary structure and function of dentin phosphoprotein peptides. Bone 95:65-75 |
| Boskey, Adele L; Imbert, Laurianne (2017) Bone quality changes associated with aging and disease: a review. Ann N Y Acad Sci 1410:93-106 |
| Boskey, Adele L; Villarreal-Ramirez, Eduardo (2016) Intrinsically disordered proteins and biomineralization. Matrix Biol 52-54:43-59 |
| Verdelis, Kostas; Szabo-Rogers, Heather L; Xu, Yang et al. (2016) Accelerated enamel mineralization in Dspp mutant mice. Matrix Biol 52-54:246-259 |
| Fang, Ping-An; Verdelis, Kostas; Yang, Xu et al. (2014) Ultrastructural organization of dentin in mice lacking dentin sialo-phosphoprotein. Connect Tissue Res 55 Suppl 1:92-6 |
| Boskey, Adele L; Verdelis, Kostas; Spevak, Lyudmila et al. (2013) Mineral and matrix changes in Brtl/+ teeth provide insights into mineralization mechanisms. Biomed Res Int 2013:295812 |
| Boskey, Adele L; Christensen, Brian; Taleb, Hayat et al. (2012) Post-translational modification of osteopontin: effects on in vitro hydroxyapatite formation and growth. Biochem Biophys Res Commun 419:333-8 |
| Poundarik, Atharva A; Diab, Tamim; Sroga, Grazyna E et al. (2012) Dilatational band formation in bone. Proc Natl Acad Sci U S A 109:19178-83 |
| Dorvee, Jason R; Boskey, Adele L; Estroff, Lara A (2012) Rediscovering Hydrogel-Based Double-Diffusion Systems for Studying Biomineralization. CrystEngComm 14:5681-5700 |
| Sfeir, Charles; Lee, Donghyun; Li, Jinhua et al. (2011) Expression of phosphophoryn is sufficient for the induction of matrix mineralization by mammalian cells. J Biol Chem 286:20228-38 |
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