Determinants of pathological mineralization.
OBJECTIVE
Physiological mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Pathological or ectopic mineralization of soft tissues, including articular cartilage and cardiovascular tissues, leads to morbidity and mortality. Recent findings suggest that the mechanisms and factors regulating physiological mineralization may be identical or similar to those regulating ectopic mineralization. Therefore, the purpose of this review is to describe the current knowledge of mechanisms and determinants that regulate physiological mineralization and how these determinants can be used to understand ectopic mineralization better.


RESULTS
Recent findings have indicated that physiological and pathological mineralization are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membrane of mineralization-competent cells. An understanding of how these vesicles initiate the physiological mineralization process may provide novel therapeutic strategies to prevent ectopic mineralization. In addition, other regulators (activators and inhibitors) of physiological mineralization have been identified and characterized, and evidence indicates that the same factors also contribute to the regulation of ectopic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiological mineralization, and if occurring after tissue injury may induce ectopic mineralization and mineralization-related differentiation events in the injured area and surrounding areas.


CONCLUSIONS
This review describes how the understanding of mechanisms and factors regulating physiological mineralization can be used to develop new therapeutic strategies to prevent pathological or ectopic mineralization events.
Kirsch
Thorsten
T
Musculoskeletal Research Laboratories, Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. tkirsch@umoa.umm.edu
D017209:Apoptosis / Q000502:physiology; D002113:Calcification, Physiologic; D002114:Calcinosis / Q000503:physiopathology*; D017610:Calcium Compounds / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007592:Joint Diseases / Q000503:physiopathology*
D017610:Calcium Compounds