Functions of biological inorganic crystals depend on their size, shape, long- and short-range order, chemical composition, specific ion environments, and spatial and chemical relationships with extracellular matrices and cells. Bone functions include contributions to mechanical characteristics, ion reservoir to maintain homeostasis of extra cellular fluids, and interactions with cells, all of which control their interactive properties and thus their mechanical and physiological roles. Data from in vitro 31P NMR, spectroscopy and imaging and in vivo experiments in living animals (eventually humans) will provide true 3-D volumetric bone mineral and bone matrix (collagen) densities from which extent of mineralization can be calculated non-invasively. This additional information has clinical implications for evaluating bone tissue in vivo in many diseases such as osteoporosis, healing of fractures and genetic disorders in children. Because the physiological and mechanical properties of bone are significantly dependent on the structure of the crystals, particularly the initial solid phase formed, studies will be pursued in situ by highly collimated synchrotron-generated wide-angle x-ray diffraction and simultaneous x-ray fluorescence (Ca concentration), FTIR imaging and microspectroscopy, and inelastic neutron scattering. We will also address the problem both theoretically and experimentally of the pre-nucleation states, viz., the chemical and structural conformation of the initial small clusters of Ca and P atoms and ions that are first bound to organic matrix constituents using molecular orbital calculations. Bone substance is a multiphase composite formed by the incorporation of brittle Ca-P nanocrystals into a soft organic matrix. Mechanical and physiological properties are also profoundly dependent on chemical and spatial relationships between the two major structural and other organic components, which will be studied by high-resolution synchrotron-generated low-angle x-ray diffraction providing the basis for mathematical modeling of spatial relationships between crystals and collagen and the spaces within the collagen fibril where the crystals are deposited. This will be accompanied -by the determination of the 3-dimensional shape and size of the crystals, determined by a new atomic force microscopy technique. Studies will continue on isolation, purification, and sequencing of phosphoproteins and sites of phosphorylation. Long-range goal wilt be preparation of single crystals of major species for crystallographic determination of molecular structure.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-SMB (02))
Program Officer
Carrington, Jill L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Zhou, Hong Wen; Burger, Christian; Wang, Hao et al. (2016) The supramolecular structure of bone: X-ray scattering analysis and lateral structure modeling. Acta Crystallogr D Struct Biol 72:986-96
Zhou, Hai-Yan; Salih, Erdjan; Glimcher, Melvin J (2010) The isolation and characterization of glycosylated phosphoproteins from herring fish bones. J Biol Chem 285:36170-8
Hofstaetter, J G; Wang, J; Yan, J et al. (2009) The effects of alendronate in the treatment of experimental osteonecrosis of the hip in adult rabbits. Osteoarthritis Cartilage 17:362-70
Rey, C; Combes, C; Drouet, C et al. (2009) Bone mineral: update on chemical composition and structure. Osteoporos Int 20:1013-21
Saad, Fawzy A; Salih, Erdjan; Glimcher, Melvin J (2008) Identification of osteopontin phosphorylation sites involved in bone remodeling and inhibition of pathological calcification. J Cell Biochem 103:852-6
Kuhn, Liisa T; Grynpas, Marc D; Rey, Christian C et al. (2008) A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages. Calcif Tissue Int 83:146-54
Burger, Christian; Zhou, Hong-Wen; Wang, Hao et al. (2008) Lateral packing of mineral crystals in bone collagen fibrils. Biophys J 95:1985-92
Cao, Haihui; Ackerman, Jerome L; Hrovat, Mirko I et al. (2008) Quantitative bone matrix density measurement by water- and fat-suppressed proton projection MRI (WASPI) with polymer calibration phantoms. Magn Reson Med 60:1433-43
Zhou, Hai-Yan (2007) Proteomic analysis of hydroxyapatite interaction proteins in bone. Ann N Y Acad Sci 1116:323-6
Wu, Yaotang; Dai, Guangping; Ackerman, Jerome L et al. (2007) Water- and fat-suppressed proton projection MRI (WASPI) of rat femur bone. Magn Reson Med 57:554-67

Showing the most recent 10 out of 25 publications