Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Organic, Inorganic and Natural Molecules in Biomineralization

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 14019

Share This Special Issue

Special Issue Editors

Prof. Dr. Slawomir Pikula

E-Mail Website
Guest Editor

Laboratory of Biochemistry of Lipids, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland
Interests: calcium homeostasis and transport; roles of annexins in the mineralization processes
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Rene Buchet

E-Mail Website
Guest Editor

Institute for Molecular and Supramolecular Chemistry and Biochemistry, Université Lyon 1, French National Centre for Scientific Research, F-69622 Lyon, France
Interests: mineralization in norm and pathoplogy; mineralization competent cells; matrix vesicles

Special Issue Information

Dear Colleagues,

Mineralized “hard” skeleton tissues have unique biomechanical properties to support a body’s weight and movement, and are a source of essential minerals required for critical body functions. Skeletal tissues regulate the levels of the inhibitory organic and inorganic molecules controlling the process of mineral crystal formation and its growth, several organic molecules being essential in the formation of mineralized microstructures, while matrix proteins have acidic regions for the binding of calcium ions in CaCO₃ crystals and interaction domains for other organic molecules. The identification of these molecules, their molecular pathways to control their levels, as well as their possible interactions with the extracellular matrix, can contribute to the development of diagnostic tools and treatments of osseous diseases.

Prof. Dr. Slawomir Pikula
Prof. Dr. Rene Buchet
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

biomineralization in norm and pathology
mineralization-competent cells
matrix vesicles
tissue nonspecific alkaline phosphatase
pathological and physiological mineralization instead of biomineralization in norm and pathology
phosphate
pyrophosphate
calcium phosphate minerals
calcium carbonate
collagen
apatite
osteopontin
fibroblast growth factor 23
parathyroid hormone
1,25 dihydroxy vitamin D
mineralization inhibitors
matrix Gla protein (MGP)
fetuin

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

17 pages, 3257 KiB

Open AccessArticle

RNAi Silencing of the Biomineralization Gene Perlucin Impairs Oyster Ability to Cope with Ocean Acidification

by Caroline Schwaner, Emmanuelle Pales Espinosa and Bassem Allam

Int. J. Mol. Sci. 2023, 24(4), 3661; https://doi.org/10.3390/ijms24043661 - 11 Feb 2023

Cited by 5 | Viewed by 1721

Abstract

Calcifying marine organisms, including the eastern oyster (Crassostrea virginica), are vulnerable to ocean acidification (OA) because it is more difficult to precipitate calcium carbonate (CaCO₃). Previous investigations of the molecular mechanisms associated with resilience to OA in C. virginica demonstrated significant differences in single nucleotide polymorphism and gene expression profiles among oysters reared under ambient and OA conditions. Converged evidence generated by both of these approaches highlighted the role of genes related to biomineralization, including perlucins. Here, gene silencing via RNA interference (RNAi) was used to evaluate the protective role of a perlucin gene under OA stress. Larvae were exposed to short dicer-substrate small interfering RNA (DsiRNA-perlucin) to silence the target gene or to one of two control treatments (control DsiRNA or seawater) before cultivation under OA (pH ~7.3) or ambient (pH ~8.2) conditions. Two transfection experiments were performed in parallel, one during fertilization and one during early larval development (6 h post-fertilization), before larval viability, size, development, and shell mineralization were monitored. Silenced oysters under acidification stress were the smallest, had shell abnormalities, and had significantly reduced shell mineralization, thereby suggesting that perlucin significantly helps larvae mitigate the effects of OA. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

15 pages, 3621 KiB

Open AccessArticle

Tunable Enzyme-Assisted Mineralization of Apatitic Calcium Phosphate by Homogeneous Catalysis

by Brittany Foley, Clément Guibert, Mohamed Selmane, Alberto Mezzetti, Caroline Lefebvre, Karim El Kirat and Jessem Landoulsi

Int. J. Mol. Sci. 2023, 24(1), 43; https://doi.org/10.3390/ijms24010043 - 20 Dec 2022

Cited by 2 | Viewed by 1257

Abstract

While it has long been mimicked by simple precipitation reactions under biologically relevant conditions, calcium phosphate biomineralization is a complex process, which is highly regulated by physicochemical factors and involves a variety of proteins and other biomolecules. Alkaline phosphatase (ALP), in particular, is a conductor of sorts, directly regulating the amount of orthophosphate ions available for mineralization. Herein, we explore enzyme-assisted mineralization in the homogeneous phase as a method for biomimetic mineralization and focus on how relevant ionic substitution types affect the obtained minerals. For this purpose, mineralization is performed over a range of enzyme substrate concentrations and fluoride concentrations at physiologically relevant conditions (pH 7.4, T = 37 °C). Refinement of X-ray diffraction data is used to study the crystallographic unit cell parameters for evidence of ionic substitution in the lattice, and infrared (IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) are used for complementary information regarding the chemical composition of the minerals. The results show the formation of substituted hydroxyapatite (HAP) after 48 h mineralization in all conditions. Interestingly, an expansion of the crystalline unit cell with an increasing concentration of the enzyme substrate is observed, with only slight changes in the particle morphology. On the contrary, by increasing the amount of fluoride, while keeping the enzyme substrate concentration unchanged, a contraction of the crystalline unit cell and the formation of elongated, well-crystallized rods are observed. Complementary IR and XPS data indicate that these trends are explained by the incorporation of substituted ions, namely CO₃²⁻ and F⁻, in the HAP lattice at different positions. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

24 pages, 2305 KiB

Open AccessArticle

Proteomic and Transcriptomic Responses Enable Clams to Correct the pH of Calcifying Fluids and Sustain Biomineralization in Acidified Environments

by Caroline Schwaner, Sarah Farhat, John Haley, Emmanuelle Pales Espinosa and Bassem Allam

Int. J. Mol. Sci. 2022, 23(24), 16066; https://doi.org/10.3390/ijms232416066 - 16 Dec 2022

Cited by 5 | Viewed by 1362

Abstract

Seawater pH and carbonate saturation are predicted to decrease dramatically by the end of the century. This process, designated ocean acidification (OA), threatens economically and ecologically important marine calcifiers, including the northern quahog (Mercenaria mercenaria). While many studies have demonstrated the adverse impacts of OA on bivalves, much less is known about mechanisms of resilience and adaptive strategies. Here, we examined clam responses to OA by evaluating cellular (hemocyte activities) and molecular (high-throughput proteomics, RNASeq) changes in hemolymph and extrapallial fluid (EPF—the site of biomineralization located between the mantle and the shell) in M. mercenaria continuously exposed to acidified (pH ~7.3; pCO₂ ~2700 ppm) and normal conditions (pH ~8.1; pCO₂ ~600 ppm) for one year. The extracellular pH of EPF and hemolymph (~7.5) was significantly higher than that of the external acidified seawater (~7.3). Under OA conditions, granulocytes (a sub-population of hemocytes important for biomineralization) were able to increase intracellular pH (by 54% in EPF and 79% in hemolymph) and calcium content (by 56% in hemolymph). The increased pH of EPF and hemolymph from clams exposed to high pCO₂ was associated with the overexpression of genes (at both the mRNA and protein levels) related to biomineralization, acid–base balance, and calcium homeostasis, suggesting that clams can use corrective mechanisms to mitigate the negative impact of OA. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

19 pages, 2922 KiB

Open AccessArticle

Shedding Light on the Role of Na,K-ATPase as a Phosphatase during Matrix-Vesicle-Mediated Mineralization

by Heitor Gobbi Sebinelli, Luiz Henrique Silva Andrilli, Bruno Zoccaratto Favarin, Marcos Aantonio Eufrasio Cruz, Maytê Bolean, Michele Fiore, Carolina Chieffo, David Magne, Andrea Magrini, Ana Paula Ramos, José Luis Millán, Saida Mebarek, Rene Buchet, Massimo Bottini and Pietro Ciancaglini

Int. J. Mol. Sci. 2022, 23(23), 15072; https://doi.org/10.3390/ijms232315072 - 01 Dec 2022

Cited by 3 | Viewed by 2137

Abstract

Matrix vesicles (MVs) contain the whole machinery necessary to initiate apatite formation in their lumen. We suspected that, in addition to tissue-nonspecific alkaline phosphatase (TNAP), Na,K,-ATPase (NKA) could be involved in supplying phopshate (P_i) in the early stages of MV-mediated mineralization. MVs were extracted from the growth plate cartilage of chicken embryos. Their average mean diameters were determined by Dynamic Light Scattering (DLS) (212 ± 19 nm) and by Atomic Force Microcopy (AFM) (180 ± 85 nm). The MVs had a specific activity for TNAP of 9.2 ± 4.6 U·mg⁻¹ confirming that the MVs were mineralization competent. The ability to hydrolyze ATP was assayed by a colorimetric method and by ³¹P NMR with and without Levamisole and SBI-425 (two TNAP inhibitors), ouabain (an NKA inhibitor), and ARL-67156 (an NTPDase1, NTPDase3 and Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) competitive inhibitor). The mineralization profile served to monitor the formation of precipitated calcium phosphate complexes, while IR spectroscopy allowed the identification of apatite. Proteoliposomes containing NKA with either dipalmitoylphosphatidylcholine (DPPC) or a mixture of 1:1 of DPPC and dipalmitoylphosphatidylethanolamine (DPPE) served to verify if the proteoliposomes were able to initiate mineral formation. Around 69–72% of the total ATP hydrolysis by MVs was inhibited by 5 mM Levamisole, which indicated that TNAP was the main enzyme hydrolyzing ATP. The addition of 0.1 mM of ARL-67156 inhibited 8–13.7% of the total ATP hydrolysis in MVs, suggesting that NTPDase1, NTPDase3, and/or NPP1 could also participate in ATP hydrolysis. Ouabain (3 mM) inhibited 3–8% of the total ATP hydrolysis by MVs, suggesting that NKA contributed only a small percentage of the total ATP hydrolysis. MVs induced mineralization via ATP hydrolysis that was significantly inhibited by Levamisole and also by cleaving TNAP from MVs, confirming that TNAP is the main enzyme hydrolyzing this substrate, while the addition of either ARL-6715 or ouabain had a lesser effect on mineralization. DPPC:DPPE (1:1)-NKA liposome in the presence of a nucleator (PS-CPLX) was more efficient in mineralizing compared with a DPPC-NKA liposome due to a better orientation of the NKA active site. Both types of proteoliposomes were able to induce apatite formation, as evidenced by the presence of the 1040 cm⁻¹ band. Taken together, the findings indicated that the hydrolysis of ATP was dominated by TNAP and other phosphatases present in MVs, while only 3–8% of the total hydrolysis of ATP could be attributed to NKA. It was hypothesized that the loss of Na/K asymmetry in MVs could be caused by a complete depletion of ATP inside MVs, impairing the maintenance of symmetry by NKA. Our study carried out on NKA-liposomes confirmed that NKA could contribute to mineral formation inside MVs, which might complement the known action of PHOSPHO1 in the MV lumen. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

16 pages, 2875 KiB

Open AccessArticle

Fabrication of Multilayered Biofunctional Material with an Enamel-like Structure

by Yu Yuan Zhang, Quan Li Li and Hai Ming Wong

Int. J. Mol. Sci. 2022, 23(22), 13810; https://doi.org/10.3390/ijms232213810 - 09 Nov 2022

Cited by 1 | Viewed by 1219

Abstract

The oral cavity is an environment with diverse bacteria; thus, antibacterial materials are crucial for treating and preventing dental diseases. There is a high demand for materials with an enamel-like architecture because of the high failure rate of dental restorations, due to the physical differences between dental materials and enamel. However, recreating the distinctive apatite composition and hierarchical architecture of enamel is challenging. The aim of this study was to synthesize a novel material with an enamel-like structure and antibacterial ability. We established a non-cell biomimetic method of evaporation-based bottom-up self-assembly combined with a layer-by-layer technique and introduced an antibacterial agent (graphene oxide) to fabricate a biofunctional material with an enamel-like architecture and antibacterial ability. Specifically, enamel-like graphene oxide-hydroxyapatite crystals, formed on a customized mineralization template, were assembled into an enamel-like prismatic structure with a highly organized orientation preferentially along the c-axis through evaporation-based bottom-up self-assembly. With the aid of layer-by-layer absorption, we then fabricated a bulk macroscopic multilayered biofunctional material with a hierarchical enamel-like architecture. This enamel-inspired biomaterial could effectively resolve the problem in dental restoration and brings new prospects for the synthesis of other enamel-inspired biomaterials. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

21 pages, 7559 KiB

Open AccessArticle

Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization

by Joanna Mroczek, Slawomir Pikula, Szymon Suski, Lilianna Weremiejczyk, Magdalena Biesaga and Agnieszka Strzelecka-Kiliszek

Int. J. Mol. Sci. 2022, 23(21), 13179; https://doi.org/10.3390/ijms232113179 - 29 Oct 2022

Cited by 5 | Viewed by 1939

Abstract

Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca²⁺ and P_i, creating an optimal environment for apatite formation. The mineralization process requires the involvement of proteins, such as annexins (Anx) and tissue-nonspecific alkaline phosphatase (TNAP), as well as low molecular-weight compounds. Apigenin, a flavonoid compound, has been reported to affect bone metabolism, but there are doubts about its mechanism of action under physiological and pathological conditions. In this report, apigenin potency to modulate annexin A6 (AnxA6)- and TNAP-mediated osteoblast mineralization was explored using three cell lines: human fetal osteoblastic hFOB 1.19, human osteosarcoma Saos-2, and human coronary artery smooth muscle cells HCASMC. We compared the mineralization competence, the morphology and composition of minerals, and the protein distribution in control and apigenin-treated cells and vesicles. The mineralization ability was monitored by AR-S/CPC analysis, and TNAP activity was determined by ELISA assay. Apigenin affected the mineral structure and modulated TNAP activity depending on the concentration. We also observed increased mineralization in Saos-2 cells. Based on TEM-EDX, we found that apigenin influenced the mineral composition. This flavonoid also disturbed the intracellular distribution of AnxA6 and TNAP, especially blocking AnxA6 aggregation and TNAP attachment to the membrane, as examined by FM analysis of cells and TEM-gold analysis of vesicles. In summary, apigenin modulates the mineralization process by regulating AnxA6 and TNAP, as well as through various effects on normal and cancer bone tissues or atherosclerotic soft tissue. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

15 pages, 19063 KiB

Open AccessArticle

Mineralization Profile of Annexin A6-Harbouring Proteoliposomes: Shedding Light on the Role of Annexin A6 on Matrix Vesicle-Mediated Mineralization

by Ekeveliny Amabile Veschi, Maytê Bolean, Luiz Henrique da Silva Andrilli, Heitor Gobbi Sebinelli, Agnieszka Strzelecka-Kiliszek, Joanna Bandorowicz-Pikula, Slawomir Pikula, Thierry Granjon, Saida Mebarek, David Magne, José Luis Millán, Ana Paula Ramos, Rene Buchet, Massimo Bottini and Pietro Ciancaglini

Int. J. Mol. Sci. 2022, 23(16), 8945; https://doi.org/10.3390/ijms23168945 - 11 Aug 2022

Cited by 5 | Viewed by 1589

Abstract

The biochemical machinery involved in matrix vesicles-mediated bone mineralization involves a specific set of lipids, enzymes, and proteins. Annexins, among their many functions, have been described as responsible for the formation and stabilization of the matrix vesicles′ nucleational core. However, the specific role of each member of the annexin family, especially in the presence of type-I collagen, remains to be clarified. To address this issue, in vitro mineralization was carried out using AnxA6 (in solution or associated to the proteoliposomes) in the presence or in the absence of type-I collagen, incubated with either amorphous calcium phosphate (ACP) or a phosphatidylserine-calcium phosphate complex (PS–CPLX) as nucleators. Proteoliposomes were composed of 1,2-dipalmitoylphosphatidylcholine (DPPC), 1,2-dipalmitoylphosphatidylcholine: 1,2-dipalmitoylphosphatidylserine (DPPC:DPPS), and DPPC:Cholesterol:DPPS to mimic the outer and the inner leaflet of the matrix vesicles membrane as well as to investigate the effect of the membrane fluidity. Kinetic parameters of mineralization were calculated from time-dependent turbidity curves of free Annexin A6 (AnxA6) and AnxA6-containing proteoliposomes dispersed in synthetic cartilage lymph. The chemical composition of the minerals formed was investigated by Fourier transform infrared spectroscopy (FTIR). Free AnxA6 and AnxA6-proteoliposomes in the presence of ACP were not able to propagate mineralization; however, poorly crystalline calcium phosphates were formed in the presence of PS–CPLX, supporting the role of annexin-calcium-phosphatidylserine complex in the formation and stabilization of the matrix vesicles’ nucleational core. We found that AnxA6 lacks nucleation propagation capacity when incorporated into liposomes in the presence of PS–CPLX and type-I collagen. This suggests that AnxA6 may interact either with phospholipids, forming a nucleational core, or with type-I collagen, albeit less efficiently, to induce the nucleation process. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Figure 1

22 pages, 3363 KiB

Open AccessArticle

Synthesis of Antibacterial Hybrid Hydroxyapatite/Collagen/Polysaccharide Bioactive Membranes and Their Effect on Osteoblast Culture

by Lucas Fabrício Bahia Nogueira, Marcos Antônio Eufrásio Cruz, Guilherme José Aguilar, Delia Rita Tapia-Blácido, Márcia Eliana da Silva Ferreira, Bianca Chieregato Maniglia, Massimo Bottini, Pietro Ciancaglini and Ana Paula Ramos

Int. J. Mol. Sci. 2022, 23(13), 7277; https://doi.org/10.3390/ijms23137277 - 30 Jun 2022

Cited by 6 | Viewed by 1728

Abstract

Inspired by the composition and confined environment provided by collagen fibrils during bone formation, this study aimed to compare two different strategies to synthesize bioactive hybrid membranes and to assess the role the organic matrix plays as physical confinement during mineral phase deposition. The hybrid membranes were prepared by (1) incorporating calcium phosphate in a biopolymeric membrane for in situ hydroxyapatite (HAp) precipitation in the interstices of the biopolymeric membrane as a confined environment (Methodology 1) or (2) adding synthetic HAp nanoparticles (SHAp) to the freshly prepared biopolymeric membrane (Methodology 2). The biopolymeric membranes were based on hydrolyzed collagen (HC) and chitosan (Cht) or κ-carrageenan (κ-carr). The hybrid membranes presented homogeneous and continuous dispersion of the mineral particles embedded in the biopolymeric membrane interstices and enhanced mechanical properties. The importance of the confined spaces in biomineralization was confirmed by controlled biomimetic HAp precipitation via Methodology 1. HAp precipitation after immersion in simulated body fluid attested that the hybrid membranes were bioactive. Hybrid membranes containing Cht were not toxic to the osteoblasts. Hybrid membranes added with silver nanoparticles (AgNPs) displayed antibacterial action against different clinically important pathogenic microorganisms. Overall, these results open simple and promising pathways to develop a new generation of bioactive hybrid membranes with controllable degradation rates and antimicrobial properties. Full article

(This article belongs to the Special Issue Organic, Inorganic and Natural Molecules in Biomineralization)

► Show Figures

Journal Menu

Journal Browser

Organic, Inorganic and Natural Molecules in Biomineralization

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI