Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification.
Clinical nephrologists are well aware of the consequences of pathologic mineralization (calcification). Several studies have found a strong association between vascular and valvular mineralization and advanced or end-stage chronic kidney disease (CKD), with shorter survival times and increased morbidity. In the cardiology community, until quite recently, ectopic mineralization was considered harmless or even beneficial. Some still assume that atherosclerotic intima mineralization stabilizes atherosclerotic plaques, thus doing more good than harm. We suggest that vascular mineralization and indeed soft tissue mineralization in general may be a way in which the body deals with certain adverse situations involving local inflammation, associated tissue damage and tissue remodeling. Ectopic soft tissue mineralization resembles physiological bone mineralization in many ways. Markers of mineralizing bone also are present during soft tissue mineralization. We postulate that it may be possible to reverse soft tissue mineralization by applying selected principles of bone catabolism, namely mineral dissolution and phagocytosis. We consider putative strategies for therapeutic intervention to maximize the clearing of calcified debris particles. In particular, we discuss the roles of the plasma protein fetuin-A/alpha2HS-glycoprotein and the mineral-binding protein osteopontin in the prevention and possible regression of mineralization in disease.
Jahnen-Dechent
Willi
W
Department of Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University Clinics, Pauwelsstrasse 30, 52074 Aachen, Germany. willi.jahnen@rwth-aachen.de
Schäfer
Cora
C
Ketteler
Markus
M
McKee
Marc D
MD
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology; D002114:Calcinosis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D008903:Minerals / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism*; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D008903:Minerals; D060749:alpha-2-HS-Glycoprotein; D053495:Osteopontin