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Mechanisms of calcification: role of collagen, polyphosphates, and phosphatase
Abstract
The nucleating properties of various collagens have been tested by determining quantitatively the minimum ion product, Ca times P, required to form calcium phosphate crystals. While most collagens require a product of 35 (mg%) 2 or greater for calcium phosphate to precipitate, some collagens extracted from tendon induce mineralization at a product of 16 (mg%) 2 . Plasma ultrafiltrate contains one or more substances which increase this minimum ion product, and therefore inhibit calcium phosphate nucleation. These substances are inactivated by alkaline phosphatase. Finally, polyphosphates, both organic and inorganic, are highly inhibitory to calcium phosphate nucleation and precipitation. It is therefore suggested that at least two mechanisms may be necessary for a tissue to mineralize: 1) the formation of a nucleating collagen and 2) the presence of phosphatase for the local destruction of the inhibitor(s) present in plasma.
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In the citing paper
“However, 1 μg P/mL “seemed to activate calcification,” which was not observed in their previous in vitro studies [6].”
From A Review of Phosphate Mineral Nucleation in Biology and Geobiology (2013) · cites this paper as [6]
In the citing paper
“In the skeletal mineralization research community, polyPs are noted to be “highly inhibitory to calcium phosphate nucleation and precipitation” [6].”
From A Review of Phosphate Mineral Nucleation in Biology and Geobiology (2013) · cites this paper as [6]
In the citing paper
“Phosphate concentrations in environmental (e.g., marine), intracellular, or extracellular (e.g., osteoid) aqueous and calcium-containing environments are too low for spontaneous, inorganic formation of a first calcium phosphate mineral from solution (nucleation).”
From A Review of Phosphate Mineral Nucleation in Biology and Geobiology (2013) · cites this paper as [6]
In the citing paper
“After describing this low supersaturation state that explains observed bone crystal growth, they continue, “however, the concentrations of these ions are not high enough to precipitate spontaneously. Some seeding mechanism seems required to initiate crystallization ” (referencing [62]).”
From A Review of Phosphate Mineral Nucleation in Biology and Geobiology (2013) · cites this paper as [6]
In the citing paper
“Fleisch and Neuman [6] noted that “extracellular fluids are supersaturated with respect to bone mineral, and that the concentrations of calcium, Pi, and hydroxyl ions are sufficiently high to support the growth of bone mineral crystals once the initial crystals have formed.””
From A Review of Phosphate Mineral Nucleation in Biology and Geobiology (2013) · cites this paper as [6]
In the citing paper
“However, the physiological concentrations of calcium and Pi [68] are not high enough to induce heterogeneous precipitation on collagen [6] or from solution [69].”
From A Review of Phosphate Mineral Nucleation in Biology and Geobiology (2013) · cites this paper as [6]
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Bisphosphonates: The first 40years
Russell, R. G. G. (2011) · Bone · doi:10.1016/j.bone.2011.04.022 · Cited by 1,164
Bisphosphonates: mechanisms of action.
Rodan, G. A., & Fleisch, H. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118722 · Cited by 930
Schlemmer, U., Frølich, W., Prieto, R., & Grases, F. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200900099 · Cited by 910
Bisphosphonates: from the laboratory to the clinic and back again
Russell, R. G. G., & Rogers, M. J. (1999) · Bone · doi:10.1016/s8756-3282(99)00116-7 · Cited by 838
Fleisch, H. A., Graham, R., Russell, R. G. G., & Francis, M. D. (1969) · Science · doi:10.1126/science.165.3899.1262 · Cited by 755
Metadata
- Authors
- Fleish, H., & Neuman, W. F.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- American Journal of Physiology-Legacy Content
- Publisher
- American Physiological Society
- Published
- 1961-06-01
- Volume
- 200
- Issue
- 6
- Pages
- 1296-1300
- ISSN
- 0002-9513 (ISSN-L)
- OpenAlex
- W2346551411
- Cited by
- 444
- References
- 0
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 11 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 5 · 2014: 7 · 2013: 10 · 2012: 2
- FWCI
- 12.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Legacy Content (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Physical Sciences › Materials Science › Biomaterials › Calcium Carbonate Crystallization and Inhibition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Keywords
- calcification, collagen, polyphosphate, alkaline phosphatase, calcium phosphate nucleation, mineralization, plasma ultrafiltrate, tendon collagen, organic phosphates, inorganic phosphate
- MeSH terms
- Calcification, Physiologic, Calcinosis, Collagen, Humans, Phosphates, Phosphoric Monoester Hydrolases, Polyphosphates
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