Current concepts of the physiology and biochemistry of calcification.

The current picture of the process of biological calcifications portrays the cells within the calcifying tissues as central factors controlling the deposition of mineral crystals in the extracellular matrix. The cell responds to hormones and second messengers, and other changes in its environment, regulating the concentration of ions within the extracellular matrix and secreting macromolecules whose properties determine the ability of the matrix to be calcified. The mitochondria within the cells accumulate calcium and phosphate, releasing these ions into the matrix as calcification progresses. Extracellular matrix vesicles, derived from the cells of some, but not all, calcifying matrices, provide sites for initial mineral deposition in many tissues. Among the macromolecules secreted by the cell, collagen provides the support for the hydroxyapatite crystals; proteoglycans serve to control the extent and/or progress of mineralization. The proteoglycans, glycoproteins, enzymes and the collagen itself, along with the cells, determine the nature of the matrix, while phosphoproteins, proteolipids, and phospholipids may serve as hydroxyapatite nucleators or as surfaces upon which apatite is deposited. but it is the interaction of many or all of these factors that determines the process of biological calcification and controls the properties of the calcified matrices.