Cited by 444Alkaline Phosphatase Research StudiesCalcium Carbonate Crystallization and InhibitionBone and Dental Protein Studies

Mechanisms of calcification: role of collagen, polyphosphates, and phosphatase

Fleish, Herbert, Neuman, William F.·1961·American Journal of Physiology-Legacy Content

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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Crossref · 10.1152/ajplegacy.1961.200.6.1296

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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].”
  • 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].”
  • 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).”
  • 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]).”
  • 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.””

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Authors
Fleish, H., & Neuman, W. F.
Affiliations
University of Rochester Medicine (US)
Venue
American Journal of Physiology-Legacy Content
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

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