4.6 Article

Molecular and biochemical approach for understanding the transition of amorphous to crystalline calcium phosphate deposits in human teeth

Journal

DENTAL MATERIALS
Volume 38, Issue 12, Pages 2014-2029

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.dental.2022.11.013

Keywords

Phase transition; Dentin; Enamel; Alkaline phosphatase; Carbonic anhydrase; Posner?s clusters; Polyphosphate; Amorphous calcium phosphate; Hydroxyapatite; Mineralization

Funding

  1. ERC Advanced Investigator Grant [268476]
  2. ERC-PoC Grants [324564, 662486, 767234]
  3. BMBF project SKIN-ENERGY [13GW0403B]
  4. European Commission [604036, 311848]
  5. International Human Frontier Science Program

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The study shows that polyphosphate can prevent the transition from amorphous CaP to crystalline CaP, and this effect can be reversed by alkaline phosphatase.
Calcium phosphate (CaP) deposition during bone mineralization starts with the aggrega-tion of Posner's clusters Ca9(PO4)6 into amorphous Ca-phosphate (ACP), which then transforms into crystalline CaP and finally maturates to hydroxyapatite (HA). Using dentin/ enamel of human teeth as a model system, we show that the physiological inorganic polymer polyphosphate (polyP), a phosphate donor in mineralization, prevents the tran-sition from amorphous to crystalline CaP at concentrations > 15 wt%. Stabilization of the amorphous phase of CaP by polyP is reversed by hydrolysis of the polymer by alkaline phosphatase (ALP), an enzyme that releases phosphate for mineralization. It is still present in calcified enamel and dentin, as shown here by immunostaining and enzyme activity measurements. The phase transfer into crystalline CaP can be prevented by the ALP in-hibitor levamisole. Besides TEM and SEM, the modulating effects of polyP and ALP on the kinetics of the phase transition from amorphous to crystalline CaP are demonstrated and confirmed by XRD and FTIR analyses. Molecular modeling studies show that the polyP chains, due to their dimensions, are able to penetrate into the channels between the Posner molecules, preventing cluster association to ACP and impairing HA crystal forma-tion.(c) 2022 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

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