10. Bone Mineralization

The mechanisms by which mineralized tissues such as bone acquire and regulate their mineral component are complex. The process of mineralization can be divided into the establishment of a primed, mineralizable matrix in which de novo mineral nucleation can occur, followed by the growth, expansion, and maturation of crystals. Perturbations in any of these events can result in bone disease and fragility. Elucidating the cellular and molecular mechanisms has been difficult because biomineralization is a combination of a physico-chemical process and a biological one. For example, phosphate participates directly in the formation of the hydroxyapatite crystals but recent studies have shown that phosphate can also directly regulate gene expression. This chapter summarizes current opinion within the field on key issues related to mineralization, such as whether mineralization is an active (cell-mediated) or a passive (physico-chemical) process and the role of cell-derived organelles/vesicles in mineralization. The molecular mediators and regulators of mineralization are reviewed and the question of whether there are unique mechanisms of mineralization in different types of bone tissue is addressed. Even though bone mineral density is currently the standard for predicting bone fragility, it is important to not only understand the inorganic component of bone, but also the organic component, as individuals with similar bone densities can have different susceptibility to fracture. These less clear properties of the skeleton that contribute to bone strength remain the focus of much investigation. THE CELLS RESPONSIBLE FOR BONE FORMATION AND MINERALIZATION Cells in the osteoblast/osteocyte lineage are responsible for bone formation...