Biologische Mineralisation vs. Pathologische Kalzifizierung –
                    die Rolle des Mineral-Chaperons Fetuin-A

Camilla Winkler; Christian Hasberg; Willi Jahnen-Dechent

doi:10.1055/a-1963-7406

Osteologie, Inhaltsverzeichnis

Osteologie 2022; 31(04): 270-279
DOI: 10.1055/a-1963-7406

Review

Biologische Mineralisation vs. Pathologische Kalzifizierung – die Rolle des Mineral-Chaperons Fetuin-A

Biological Mineralisation vs. Pathological Calcification – the Role of the Mineral Chaperone Fetuin-A

Camilla Winkler

¹Zell- und Molekularbiologie an Grenzflächen, Medizinische Fakultät, RWTH Aachen University, Aachen, Germany

,

Christian Hasberg

¹Zell- und Molekularbiologie an Grenzflächen, Medizinische Fakultät, RWTH Aachen University, Aachen, Germany

,

Willi Jahnen-Dechent

¹Zell- und Molekularbiologie an Grenzflächen, Medizinische Fakultät, RWTH Aachen University, Aachen, Germany

› Institutsangaben

Abstract

Zusammenfassung

Die Mineralien Kalzium und Phosphat sind für den Zellstoffwechsel aller lebenden Organismen unverzichtbar. Beide Ionen kommen in biologischen Flüssigkeiten normalerweise in millimolaren Konzentrationen vor. Dies führt zu einem Löslichkeits- und Transportproblem, da Kalziumphosphate in Wasser kaum löslich sind und leicht aus übersättigten Lösungen ausfallen. Mineral-Chaperone stabilisieren Mineral als Kolloid und ermöglichen so den Transport und die Clearance nominell übersättigter Mineral-Lösungen. Am Beispiel des Plasmaproteins Fetuin-A erklären wir die Rolle systemischer Mineral-Chaperone, insbesondere bei gestörtem Mineralstoffwechsel. Wir beschreiben den Stoffwechsel kolloidaler Protein-Mineralkomplexen, die in Anlehnung an Lipoprotein-Partikel Calciprotein-Partikel, kurz CPP genannt werden. Wir behandeln die Rolle von CPP bei der physiologischen Knochenbildung und der pathologischen Kalzifizierung. Wir nennen wesentliche Regulatoren von Ossifizierung und Kalzifizierung auf Ebene der Gene, Proteine und Metaboliten. Zuletzt erörtern wir mögliche Therapien von Kalzifizierung anhand eines hierarchischen Modells von mineralinduziertem Stress.

Abstract

The minerals calcium and phosphate are essential for cell metabolism in all living organisms. Both ions normally occur in biological fluids in millimolar concentrations. This leads to a solubility and transport problem, as calcium phosphates are poorly soluble in water and readily precipitate from supersaturated solutions. Mineral chaperones stabilize mineral as a colloid, allowing transport and clearance of nominally supersaturated mineral solutions. Using the plasma protein fetuin-A as an example, we explain the role of systemic mineral chaperones, particularly in the presence of impaired mineral metabolism. We describe the metabolism of colloidal protein-mineral complexes, which we have named calciprotein particles, or CPP, in reference to lipoprotein particles. We address the role of CPP in physiological bone formation and pathological calcification. We name key regulators of ossification and calcification at the gene, protein, and metabolite levels. Last, we discuss potential therapies of calcification using a hierarchical model of mineral-induced stress.

Schlüsselwörter

Biomineralisation - Kalzifizierung - Mineral Chaperone - Heterotope Ossifikation - Fetuin-A

Key words

Biomineralization - Calcification - Mineral Chaperones - Heterotopic Ossification - Fetuin-A

Volltext

Referenzen

Literatur
1 Jahnen-Dechent W, Moshkova I. “It’s Time To Get Leave,” Says Fetuin-A to Calcium Phosphate. Frontiers Young Minds 2021; 9: 551203
2 Boskey AL. Calcified Tissues: Chemistry and Biochemistry. In: Nordin BEC, Hrsg. Calcium in Human Biology. 1988: 171-186
3 [Anonym]. Protein Kinase Inhibitors Im Internet: https://www.ncbi.nlm.nih.gov/pubmed/31643906 Stand: 20 Sep 2021
4 Brown MRW, Kornberg A. Inorganic polyphosphate in the origin and survival of species. Proc National Acad Sci 2004; 101: 16085-16087 PMID - 15520374
5 LeGeros RZ. Formation and transformation of calcium phosphates: relevance to vascular calcification. Zeitschrift Für Kardiologie 2001; 90: 116-124 PMID - 11374023
6 Cölfen H. A crystal-clear view. Nat Mater 2010; 9: 960-961 PMID - 21102512
7 Hénaut L, Massy ZA. Magnesium as a Calcification Inhibitor. Adv Chronic Kidney D 2018; 25: 281-290 PMID - 29793668
8 Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J 2012; 5: i3-i14 PMID - 26069819
9 Orriss IR, Arnett TR, Russell RGG. Pyrophosphate: a key inhibitor of mineralisation. Curr Opin Pharmacol 2016; 28: 57-68 PMID - 27061894
10 Yoreo JD, Whitelam S. Nucleation in atomic, molecular, and colloidal systems. Mrs Bull 2016; 41: 357-360
11 Espinosa JR, Vega C, Valeriani C. et al. Heterogeneous versus homogeneous crystal nucleation of hard spheres. Soft Matter 2019; 15: 9625-9631 PMID - 31613303
12 Reznikov N, Steele JAM, Fratzl P. et al. A materials science vision of extracellular matrix mineralization. Nat Rev Mater 2016; 1: 16041
13 Hazen RM, Papineau D, Bleeker W. et al. Review Paper. Mineral evolution. Am Mineral 2008; 93: 1693-1720 PMID - 9523714
14 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 2008; 86: 379-389 PMID - 18080808
15 Cross KJ, Huq NL, Palamara JE. et al. Physicochemical Characterization of Casein Phosphopeptide-Amorphous Calcium Phosphate Nanocomplexes*. J Biol Chem 2005; 280: 15362-15369 PMID - 15657053
16 Jahnen-Dechent W, Büscher A, Köppert S. et al. Mud in the blood: the role of protein-mineral complexes and extracellular vesicles in biomineralisation and calcification. J Struct Biol 2020; 212: 107577 PMID - 32711043
17 Khavandgar Z, Roman H, Li J. et al. Elastin Haploinsufficiency Impedes the Progression of Arterial Calcification in MGP-Deficient Mice. J Bone Miner Res 2014; 29: 327-337 PMID - 23857752
18 Hunter GK, Goldberg HA. Nucleation of hydroxyapatite by bone sialoprotein. Proc National Acad Sci 1996; 90: 8562-8565 PMID - 8397409
19 Moradian-Oldak J, George A. Biomineralization of Enamel and Dentin Mediated by Matrix Proteins. J Dent Res 2021; 100: 1020-1029 PMID - 34151644
20 Chuang S-F, Chen Y-H, Ma PX. et al. Dentin Sialoprotein/Phosphophoryn (DSP/PP) as Bio-Inductive Materials for Direct Pulp Capping. Polymers-basel 2022; 14: 3656 PMID - 36080731
21 Jahnen-Dechent W. „Lot’s Wife’s Problem” gelöst? Regulation der biologischen Calcifizierung. Biospektrum 2004; 2004: 254-257
22 Arnold A, Dennison E, Kovacs CS. et al. Hormonal regulation of biomineralization. Nat Rev Endocrinol 2021; 17: 261-275 PMID - 33727709
23 Kuro-o M. The Klotho proteins in health and disease. Nat Rev Nephrol 2019; 15: 27-44 PMID - 30455427
24 Jahnen-Dechent W, Heiss A, Schäfer C. et al. Fetuin-A Regulation of Calcified Matrix Metabolism. Circ Res 2011; 108: 1494-1509 PMID - 21659653
25 Lee C, Bongcam-Rudloff E, Sollner C. et al. Type 3 cystatins; fetuins, kininogen and histidine-rich glycoprotein. Front Biosci 2009; 2911 PMID - 19273244
26 Cuppari A, Körschgen H, Fahrenkamp D. et al. Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition. Iucrj 2019; 6: 317-330 PMID - 30867929
27 Babler A, Schmitz C, Buescher A. et al. Microvasculopathy and soft tissue calcification in mice are governed by fetuin-A, magnesium and pyrophosphate. Plos One 2020; 15: e0228938 PMID - 32074140
28 Herrmann M, Babler A, Moshkova I. et al. Lumenal calcification and microvasculopathy in fetuin-A-deficient mice lead to multiple organ morbidity. Plos One 2020; 15: e0228503 PMID - 32074120
29 Schäfer C, Heiss A, Schwarz A. et al. The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112: 357-366 PMID - 12897203
30 Tiong MK, Cai MMX, Toussaint ND. et al. Effect of nutritional calcium and phosphate loading on calciprotein particle kinetics in adults with normal and impaired kidney function. Sci Rep-uk 2022; 12: 7358 PMID - 35513558
31 Koeppert S, Ghallab A, Peglow S. et al. Live Imaging of Calciprotein Particle Clearance and Receptor Mediated Uptake: Role of Calciprotein Monomers. Frontiers Cell Dev Biology 2021; 9: 633925 PMID - 33996793
32 Köppert S, Büscher A, Babler A. et al. Cellular Clearance and Biological Activity of Calciprotein Particles Depend on Their Maturation State and Crystallinity. Front Immunol 2018; 9: 1991 PMID - 30233585
33 Nakamura K, Isoyama N, Nakayama Y. et al. Association between amorphous calcium-phosphate ratios in circulating calciprotein particles and prognostic biomarkers in hemodialysis patients. Sci Rep-uk 2022; 12: 13030 PMID - 35906396
34 Loohuis KMO, Jahnen-Dechent W, van Dorp W. The Case | Milky ascites is not always chylous. Kidney Int 2010; 77: 77-78 PMID - 20010886
35 Herrmann M, Schäfer C, Heiss A. et al. Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A. Circ Res 2012; 111: 575-584 PMID - 22753077
36 Heiss A, DuChesne A, Denecke B. et al. structural basis of calcification inhibition by α2-hs glycoprotein/fetuin-a formation of colloidal calciprotein particles*. J Biol Chem 2003; 278: 13333-13341 PMID - 12556469
37 Akiva A, Nelkenbaum O, Schertel A. et al. Intercellular pathways from the vasculature to the forming bone in the zebrafish larval caudal fin: Possible role in bone formation. J Struct Biol 2019; 206: 139-148 PMID - 30858049
38 Akiyama K-i MiuraY, Hayashi H. et al. Calciprotein particles regulate fibroblast growth factor-23 expression in osteoblasts. Kidney Int 2020; 97: 702-712 PMID - 32001068
39 Kerschnitzki M, Akiva A, Shoham AB. et al. Transport of membrane-bound mineral particles in blood vessels during chicken embryonic bone development. Bone 2016; 83: 65-72 PMID - 26481471
40 Price PA, Caputo J, Williamson M. Bone origin of the serum complex of calcium, phosphate, fetuin, and matrix Gla protein: biochemical evidence for the cancellous bone-remodeling compartment. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research PMID - 12096831 2002; 17 1171 1179
41 Dickson IR, Poole AR, Veis A. Localisation of plasma α2HS glycoprotein in mineralising human bone. Nature 1975; 256: 430-432 PMID - 49853
42 Ashton BA, Höhling HJ, Triffitt JT. Plasma proteins present in human cortical bone: Enrichment of theαHS-glycoprotein. Calc Tiss Res 1976; 22: 27-33 PMID - 1000340
43 Brylka LJ, Köppert S, Babler A. et al. Post-weaning epiphysiolysis causes distal femur dysplasia and foreshortened hindlimbs in fetuin-A-deficient mice. Plos One 2017; 12: e0187030 PMID - 29088242
44 Aghagolzadeh P, Bachtler M, Bijarnia R. et al. Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α. Atherosclerosis 2016; 251: 404-414 PMID - 27289275
45 Heiss A, Jahnen-Dechent W, Endo H. et al. Structural dynamics of a colloidal protein-mineral complex bestowing on calcium phosphate a high solubility in biological fluids. Biointerphases 2007; 2: 16-20 PMID - 20408632
46 Heiss A, Pipich V, Jahnen-Dechent W. et al. Fetuin-A Is a Mineral Carrier Protein: Small Angle Neutron Scattering Provides New Insight on Fetuin-A Controlled Calcification Inhibition. Biophys J 2010; 99: 3986-3995 PMID - 21156141
47 Rochette CN, Rosenfeldt S, Heiss A. et al. A Shielding Topology Stabilizes the Early Stage Protein–Mineral Complexes of Fetuin-A and Calcium Phosphate: A Time-Resolved Small-Angle X-ray Study. Chembiochem 2009; 10: 735-740 PMID - 19222044
48 Heiss A, Eckert T, Aretz A. et al. Hierarchical Role of Fetuin-A and Acidic Serum Proteins in the Formation and Stabilization of Calcium Phosphate Particles. J Biol Chem 2008; 283: 14815-14825 PMID - 18364352
49 Price PA, Lim JE. The Inhibition of Calcium Phosphate Precipitation by Fetuin Is Accompanied by the Formation of a Fetuin-Mineral Complex*. J Biol Chem 2003; 278: 22144-22152 PMID - 12676929
50 Wald J, Wiese S, Eckert T. et al. Formation and stability kinetics of calcium phosphate –fetuin-A colloidal particles probed by time-resolved dynamic light scattering. Soft Matter 2011; 7: 2869-2874
51 Salhotra A, Shah HN, Levi B. et al. Mechanisms of bone development and repair. Nat Rev Mol Cell Bio 2020; 21: 696-711 PMID - 32901139
52 Soltanoff CS, Yang S, Chen W. et al. Signaling Networks that Control the Lineage Commitment and Differentiation of Bone Cells. Crit Rev Eukar Gene 2009; 19: 1-46 PMID - 19191755
53 Reynolds JL, Skepper JN, McNair R. et al. Multifunctional Roles for Serum Protein Fetuin-A in Inhibition of Human Vascular Smooth Muscle Cell Calcification. J Am Soc Nephrol 2005; 16: 2920-2930 PMID - 16093453
54 Fratzl P. Bone fracture: When the cracks begin to show. Nat Mater 2008; 7: 610-612 PMID - 18654582
55 Whyte MP, Madson KL, Phillips D. et al. Asfotase alfa therapy for children with hypophosphatasia. Jci Insight 2016; 1: e85971 PMID - 27699270
56 Pedraza CE, Nikolcheva LG, Kaartinen MT. et al. Osteopontin functions as an opsonin and facilitates phagocytosis by macrophages of hydroxyapatite-coated microspheres: Implications for bone wound healing. Bone 2008; 43: 708-716 PMID - 18656563
57 Cobb AM, Yusoff S, Hayward R. et al. Runx2 (Runt-Related Transcription Factor 2) Links the DNA Damage Response to Osteogenic Reprogramming and Apoptosis of Vascular Smooth Muscle Cells. Arteriosclerosis Thrombosis Vasc Biology 2020; 41: 1339-1357 PMID - 33356386
58 Kaplan FS, Pignolo RJ, Shore EM. Granting immunity to FOP and catching heterotopic ossification in the Act. Semin Cell Dev Biol 2016; 49: 30-36 PMID - 26706149
59 Zeckey C, Hildebrand F, Mommsen P. et al. Risk of symptomatic heterotopic ossification following plate osteosynthesis in multiple trauma patients: an analysis in a level-1 trauma centre. Scand J Trauma Resusc Emerg Medicine 2009; 17: 55 PMID - 19825174
60 Eisenstein N, Stapley S, Grover L. Post-Traumatic Heterotopic Ossification: An Old Problem in Need of New Solutions. J Orthop Res 2018; 36: 1061-1068 PMID - 29193256
61 Alfieri KA, Forsberg JA, Potter BK. Blast injuries and heterotopic ossification. Bone Jt Res 2012; 1: 174-179 PMID - 23610689
62 Shimono K, Morrison TN, Tung WE. et al. Inhibition of ectopic bone formation by a selective retinoic acid receptor α-agonist: A new therapy for heterotopic ossification?. J Orthopaed Res 2010; 28: 271-277 PMID - 19725108
63 Potter BK, Burns TC, Lacap AP. et al. Heterotopic Ossification Following Traumatic and Combat-Related Amputations. J Bone Jt Surg 2007; 89: 476-486 PMID - 17332095
64 Haran MJ, Bhuta T, Lee BSB. Pharmacological interventions for treating acute heterotopic ossification. Cochrane Db Syst Rev 2010; CD003321 PMID - 20464723
65 Meyers C, Lisiecki J, Miller S. et al. Heterotopic Ossification: A Comprehensive Review. Jbmr Plus 2019; 3: e10172 PMID - 31044187
66 Takeda S. Central Control of Bone Remodelling. J Neuroendocrinol 2008; 20: 802-807 PMID - 18601702
67 Gugala Z, Olmsted-Davis EA, Xiong Y. et al. Trauma-Induced Heterotopic Ossification Regulates the Blood-Nerve Barrier. Front Neurol 2018; 9: 408 PMID - 29922221
68 Hadad MJ, Stonko DS, DiBrito S. et al. Extensive Abdominal Heterotopic Ossification in a Patient with Distant Penetrating Trauma. ACS Case Reviews in Surgery 2020; 3: 47-50
69 Tuzmen C, Verdelis K, Weiss L. et al. Crosstalk between substance P and calcitonin gene-related peptide during heterotopic ossification in murine Achilles tendon. J Orthop Res 2018; 36: 1444-1455 PMID - 29227562
70 Pape HC, Lehmann U. Griensven Mv et al. Heterotopic ossifications in patients after severe blunt trauma with and without head trauma: incidence and patterns of distribution. Journal of orthopaedic trauma 2001; 15 229 237
71 Giannoudis PV, Mushtaq S, Harwood P. et al. Accelerated bone healing and excessive callus formation in patients with femoral fracture and head injury. Inj 2006; 37: S18-S24 PMID - 16963358
72 Khallaf FG, Kehinde EO, Hussein S. Bone Healing and Hormonal Bioassay in Patients with Long-Bone Fractures and Concomitant Head Injury. Med Prin Pract 2016; 25: 336-342 PMID - 26954461
73 Wildburger R, Zarkovic N, Egger G. et al. Basic fibroblast growth factor (BFGF) immunoreactivity as a possible link between head injury and impaired bone fracture healing. Bone Miner 1994; 27: 183-192 PMID - 7696886
74 Virchow R. Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre. 4. Aufl. 1871
75 Mohr W, Görz E. Imitiert die arteriosklerotische Gefäßwandverkalkung die Osteogenese? Pathomorphologische Untersuchungen an arteriosklerotischen Beeten. Zeitschrift Für Kardiologie 2002; 91: 212-232 PMID - 12001537
76 Chaudhuri O, Cooper-White J, Janmey PA. et al. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 2020; 584: 535-546
77 Fitzpatrick LA, Turner RT, Ritman ER. Endochondral Bone Formation in the Heart: A Possible Mechanism of Coronary Calcification. Endocrinology 2003; 144: 2214-2219 PMID - 12746277
78 Qiao J-H, Mertens RB, Fishbein MC. et al. Cartilaginous metaplasia in calcified diabetic peripheral vascular disease: Morphologic evidence of enchondral ossification. Hum Pathol 2003; 34: 402-407 PMID - 12733123
79 Belavgeni A, Meyer C, Stumpf J. et al. Ferroptosis and Necroptosis in the Kidney. Cell Chem Biol 2020; 27: 448-462 PMID - 32302582
80 Ghadially FN. As You Like It, Part 3: A Critique and Historical Review of Calcification as Seen with the Electron Microscope. Ultrastruct Pathol 2001; 25: 243-267 PMID - 11465480
81 Kim KM. Apoptosis and calcification. Scanning Microscopy 1995; 9: 1137-1175 discussion 1175-1138
82 Bonucci E, Derenzini M, Marinozzi V. The organic-inorganic relationship in calcified mitochondria. J Cell Biology 1973; 59 185 211
83 Ghadially FN. As You Like It. Ultrastruct Pathol 1997; 21: 211-226 PMID - 9183822
84 Ghadially FN. As You Like It, Part 2: A Critique and Historical Review of the Electron Microscopy Literature. Ultrastruct Pathol 1999; 23: 1-17 PMID - 10086912
85 Rudloff S, Jahnen-Dechent W, Huynh-Do U. Tissue chaperoning—the expanded functions of fetuin-A beyond inhibition of systemic calcification. Pflügers Archiv - European J Physiology 2022; 474: 949-962 PMID - 35403906
86 Noels H, Boor P, Goettsch C. et al. The new SFB/TRR219 Research Centre. Eur Heart J 2018; 39: 975-977 PMID - 29579229
87 Mönckeberg JG. Über die reine Mediaverkalkung der Extremitätenarterien und ihr Verhalten zur Arteriosklerose. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin 1903; 171: 141-167
88 Nakazato J, Hoshide S, Wake M. et al. Association of calciprotein particles measured by a new method with coronary artery plaque in patients with coronary artery disease: A cross-sectional study. J Cardiol 2019; 74: 428-435 PMID - 31101573
89 Ernst E. Chelation therapy for peripheral arterial occlusive disease: a systematic review. Circulation 1997; 96 1031 1033