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Determinants of pathologic mineralization.

Physiologic mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Mineralization has to be controlled and restricted to specific regions. If the mineralization process occurs in regions that normally do not mineralize, there can be severe consequences (pathologic or ectopic mineralization). Recent findings have indicated that physiologic and pathologic mineralization events are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membranes of mineralization-competent cells. The understanding of how these vesicles are released from the plasma membrane and initiate the mineralization process may provide novel therapeutic strategies to prevent pathologic mineralization. In addition, other regulators (activators and inhibitors) of physiologic mineralization have been identified and characterized, and there is evidence that the same factors also contribute to the regulation of pathologic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiologic mineralization and if occurring after tissue injury may induce pathologic mineralization and mineralization-related differentiation events in the injured and surrounding areas. This review describes how the understanding of mechanisms and factors regulating physiologic mineralization can be used to develop new therapeutic strategies to prevent pathologic or ectopic mineralization events.