Mechanism of De Novo Mineral Formation by Matrix Vesicles

Matrix vesicles (MV) induce mineralization by compartmentalization of ion accumulation and crystal nucleation within membrane-enclosed extracellular microstructures. MV derive from cell surface microvilli by processes that cause selective enrichment of specific proteins, enzymes, lipids, and electrolytes. Incubated in synthetic cartilage lymph (SCL), MV accumulate Ca2+ and Pi, inducing mineral formation in a sequence of stages that can be altered by specific affectors. Rapid uptake of mineral ions by MV precedes formation of the first crystalline phase, octacalcium phosphate (OCP), which later converts to apatite (HAP). Early uptake of Ca2+ and Pi by MV is pH and protease sensitive, and is stimulated by o-phenanthroline (OP), a Zn2+ chelator. Recent studies reveal that a quantitatively major group of MV proteins bind to Ca2+ with high affinity in a lipid-dependent manner. These MV proteins appear to be involved in transport and accumulation of Ca2+ and Pi by MV, and may catalyze nucleation of the first mineral phase.