Mechanisms of pathologic calcification

Pathologic calcification usually is initiated by the biologic membranes of mitochondria or matrix vesicles. Mitochondria frequently initiate intracellular calcification. Matrix vesicles, derived from the outer membrane of cells by budding or cell disruption, initiate extracellular calcification in calcific tendonitis, apatite-deposition osteoarthritis, atherosclerosis, cardiac valvular calcification, tympanosclerosis, and other calcific diseases. Matrix vesicles and mitochondria usually initiate calcification through the interaction of phosphatase enzymes with calcium-binding phospholipids, both of which are membrane-bound. Hydroxyapatite (HA) crystals are formed first within the protective microenvironment of the membrane-enclosed microspace. Once formed and exposed to the extracellular fluid, HA crystals can serve as nuclei or templates, thus supporting progressive, autocatalytic mineral crystal proliferation.