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Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification

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Abstract

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.

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Acknowledgments

The original research discussed and presented in this manuscript was funded by the Deutsche Forschungsgemeinschaft and the Interdisciplinary Center for Clinical Research IZKF Biomat within the Medical Faculty of RWTH Aachen University (WJD, MK) and by the Canadian Institutes of Health Research (MDM) and the National Institutes of Health USA (MDM). The authors thank L. Malynowsky for assistance with the microscopy, and G. Karsenty, T. Schinke, M. Murshed, A. Nanci, C. Murry, and C. Giachelli for scientific collaborations and discussions related to the themes of this work.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University Clinics, Pauwelsstrasse 30, 52074, Aachen, Germany

    Willi Jahnen-Dechent & Cora Schäfer

  2. Medical Clinic III, Klinikum Coburg gGmbH, Ketschendorfer Str. 33, 96450, Coburg, Germany

    Markus Ketteler

  3. Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A 2B2, Canada

    Marc D. McKee

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  1. Willi Jahnen-Dechent
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  2. Cora Schäfer
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  4. Marc D. McKee
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Correspondence to Willi Jahnen-Dechent.

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Jahnen-Dechent, W., Schäfer, C., Ketteler, M. et al. Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification. J Mol Med 86, 379–389 (2008). https://doi.org/10.1007/s00109-007-0294-y

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