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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At 1 μg phosphorus/mL, polyphosphate seemed to activate calcification in cultured chick embryo femurs.
“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]
Polyphosphates are highly inhibitory to calcium phosphate nucleation and precipitation.
“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]
Phosphate concentrations in environmental, intracellular, or extracellular aqueous and calcium-containing environments are too low for spontaneous inorganic formation of a first calcium phosphate mineral from solution.
“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]
The concentrations of calcium, inorganic phosphate, and hydroxyl ions are not high enough to precipitate spontaneously, and some seeding mechanism seems required to initiate crystallization.
“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]
Extracellular fluids are supersaturated with respect to bone mineral, and the concentrations of calcium, inorganic phosphate, and hydroxyl ions are sufficiently high to support the growth of bone mineral crystals once initial crystals have formed.
“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]
Physiological concentrations of calcium and inorganic phosphate are not high enough to induce heterogeneous precipitation on collagen or from solution.
“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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- 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
- Health Sciences › Medicine › Rheumatology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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