How does osteocalcin lacking γ-glutamic groups affect biomimetic apatite formation and what can we say about its structure in mineral-bound form?

Iline-Vul, Taly; Kulpanovich, Alexey; Nadav-Tsubery, Merav; Semionov, Artyom; Keinan‐Adamsky, Keren; Goobes, Gil

doi:10.1016/j.jsb.2019.04.014

Cited by 12 publications

(17 citation statements)

References 57 publications

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“…The latter result is all the more noteworthy when considering the challenges related to performing 2D 1 H- 43 Ca HETCOR analyses at natural abundance (0.14 %), due to the unfavorable NMR properties of calcium-43 ( Table 1). structure of bone (by looking at octacalcium phosphate derived phases, [65,66] or at the adsorption of non-collagenous bone proteins like osteocalcin on hydroxyapatite [67]), or to help understand how ACPs can be stabilized in presence of proteins. [68] In the latter case, Gésan-Guiziou and co-workers (Table 1), which despite their unfavourable NMR properties are likely to provide valuable information.…”

Section: Calcium Phosphate Surfaces and Interfacesmentioning

confidence: 99%

Recent directions in the solid-state NMR study of synthetic and natural calcium phosphates

Gervais

Bonhomme

Laurencin

2020

Solid State Nuclear Magnetic Resonance

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Materials containing a calcium phosphate component have been the subject of much interest to NMR spectroscopists, especially in view of understanding the structure and properties of mineralized tissues like bone and teeth, and of developing synthetic biomaterials for bone regeneration. Here, we present a selection of recent developments in their structural characterization using advanced solid state NMR experiments, highlighting the level of insight which can now be accessed. 1 H, 31 P, 43 Ca, 17 O  Ultra-high magnetic fields  Dynamic Nuclear Polarization  Micro-imaging under MAS  Computational modeling  Isotopic labeling Monetite CaHPO 4 Octacalcium-phosphate (OCP) Ca 8 (HPO 4) 2 (PO 4) 4 .5H 2 O t-Ca 2 (P 2 O 7).2H 2 O m-Ca 2 (P 2 O 7).4H 2 O Apatitic-like layer Hydrated layer Apatitic-like layer Examples of Calcium-orthophosphates Examples of Calcium-pyrophosphates

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Section: Calcium Phosphate Surfaces and Interfacesmentioning

confidence: 99%

Recent directions in the solid-state NMR study of synthetic and natural calcium phosphates

Gervais

Bonhomme

Laurencin

2020

Solid State Nuclear Magnetic Resonance

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“…Interestingly, the NMR properties of the phosphates in this layer are sensitive to the protein used in the mineral synthesis. Here, for example, the disordered phosphate peak in HAP•qOPN is narrower than in HAP, indicating that the protein acts to decrease the degree of disorder in the surface layer, as was observed for umOC 26 . The reverse effect was observed for ON29, whereby the peptide induced greater disorder in this layer 27 .…”

Section: Solid State Nmr Analysis Of the Crystalline And Disordered Mmentioning

confidence: 54%

“…Previous TGA measurements of HAP•ON29 showed that the peptide constitutes 4.8 weight% (1.6 mol%) of the material. Similarly, TGA of HAP•umOC showed that umOC constitutes 8.0 weight% of the material (1.4 mol%) 26,28 . Molar content of qOPN in the protein-mineral composite formed is much lower than ON29 or umOC.…”

Section: Discussion Influence Of Qopn and Other Non-collagenous Protmentioning

confidence: 91%

“…In addition, partially disordered phosphates excited by OH − protons, denoted "species II", (peak at 3.3 ppm FWHM 3.3-3.5 ppm) and partially ordered phosphates excited by water protons, denoted "species III", (peak at 2.6 ppm FWHM 2.7-3.0 ppm) are also detected. The latter two new phosphate species, recognized recently 26,27 , define an intermediate mineral phase which resides spatially between the bulk apatite crystal and outer disordered phase. This phase contains PO 4 3− and HPO 4 2− ions characterized by transitional order (or disorder) compared to the crystalline and amorphous phases, as can be noticed from their intermediate linewidths.…”

Section: Discussion Influence Of Qopn and Other Non-collagenous Protmentioning

confidence: 99%

“…Recently, we have studied the regulatory effect on the in vitro crystallization of bone-mimetic apatite of two bone-associated polypeptides. Osteocalcin, unmodified posttranslationally 26 (umOC) and ON29, a peptide from osteonectin's mineral binding domain 27 exhibited markedly different effects on the process of crystallization. Apart from their disparate effects on the morphology and crystallinity of apatite, we could show that the two biomolecules also intervened with the thickness and composition of the amorphous mineral layer, coating the apatite crystallites; ON29 induced thickening of this layer, while OC promoted the reverse.…”

Section: Biological Activity Of Non-colagenous Proteinsmentioning

confidence: 99%

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Osteopontin regulates biomimetic calcium phosphate crystallization from disordered mineral layers covering apatite crystallites

Iline-Vul

Nanda

Mateos

et al. 2020

Sci Rep

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Details of apatite formation and development in bone below the nanometer scale remain enigmatic. Regulation of mineralization was shown to be governed by the activity of non-collagenous proteins with many bone diseases stemming from improper activity of these proteins. Apatite crystal growth inhibition or enhancement is thought to involve direct interaction of these proteins with exposed faces of apatite crystals. However, experimental evidence of the molecular binding events that occur and that allow these proteins to exert their functions are lacking. Moreover, recent high-resolution measurements of apatite crystallites in bone have shown that individual crystallites are covered by a persistent layer of amorphous calcium phosphate. It is therefore unclear whether non-collagenous proteins can interact with the faces of the mineral crystallites directly and what are the consequences of the presence of a disordered mineral layer to their functionality. In this work, the regulatory effect of recombinant osteopontin on biomimetic apatite is shown to produce platelet-shaped apatite crystallites with disordered layers coating them. The protein is also shown to regulate the content and properties of the disordered mineral phase (and sublayers within it). Through solid-state NMR atomic carbon-phosphorous distance measurements, the protein is shown to be located in the disordered phases, reaching out to interact with the surfaces of the crystals only through very few sidechains. These observations suggest that non-phosphorylated osteopontin acts as regulator of the coating mineral layers and exerts its effect on apatite crystal growth processes mostly from afar with a limited number of contact points with the crystal.

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Structural and mutational analyses of decarboxylated osteocalcin provide insight into its adiponectin‐inducing activity

et al. 2023

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An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high‐resolution X‐ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α‐helix structure of native osteocalcin with three γ‐carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site‐directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin‐inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin.

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How does osteocalcin lacking γ-glutamic groups affect biomimetic apatite formation and what can we say about its structure in mineral-bound form?

Cited by 12 publications

References 57 publications

Recent directions in the solid-state NMR study of synthetic and natural calcium phosphates

Recent directions in the solid-state NMR study of synthetic and natural calcium phosphates

Osteopontin regulates biomimetic calcium phosphate crystallization from disordered mineral layers covering apatite crystallites

Structural and mutational analyses of decarboxylated osteocalcin provide insight into its adiponectin‐inducing activity

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