The role of matrix vesicles in physiological and pathological calcification

Purpose of review: To summarize what is known of the mechanisms by which normal and pathologic biomineralization are initiated. An understanding of how cells initiate and control mineralization via extracellular matrix vesicles may lead to new methods to control unwanted calcification in calcific diseases. Recent findings: There is widespread agreement that the normal mineralization of cartilage, bone and dentin begins with the deposition of CaPO4 in the form of hydroxyapatite crystals within the membranes of matrix vesicles. Recent findings indicate that skeletal matrix vesicles arise by budding from the surfaces of viable rather than apoptotic growth-plate chondrocytes. Matrix vesicles, lacking alkaline phosphatase or nucleoside triphosphate pyrophosphohydrolase, exhibit failed mineralization in genetically deficient mice. A new phosphatase, PHOSPHO1, is enriched in skeletal matrix vesicles, and stimulates matrix vesicle-initiated mineralization. Matrix vesicles initiate arterial calcification in atherosclerosis. The likelihood of a serious heart attack in patients with coronary atherosclerosis is greatly increased by the presence of calcification in coronary arteries. In breast cancer, the mineralization pattern in mammograms is initiated by matrix vesicle-like vesicles. Summary: Matrix vesicles initiate and promote normal skeletal calcification, and a variety of forms of pathological calcification.