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Molecular Mechanisms of Biomineralization in Healthy and Pathological Bone Tissues

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15435

Special Issue Editors


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Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy
Interests: X-ray synchrotron-based techniques; biomineralization; osteoblastic differentiation; 3D cell culture; cellular imaging
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Guest Editor
CNRS Research Director Centre de Resonance Magnetique Biologique et Medicale
Interests: MRI; microarchitecture; bone; skeletal muscle; ultra high field MRI

Special Issue Information

Dear Colleagues,

Biomineralization refers to the process by which living systems generate organized mineral crystals. It represents an extremely widespread phenomenon culminating with hydroxyapatite formation. Biomineralization is a lifelong process, playing a key role in bone formation, repair, and remodeling. Bone mineralization depends upon the complex crosstalk between osteoclasts, osteoblasts, and osteocytes. The complexity of bone organization can be tackled across multiple length scales, and this structural hierarchy governs its mechanical behavior. The degree of bone mineralization, assessed by the bone mineral density, the microarchitecture, and the characteristics of the mineral deposits (apatite crystals), is a major determinant of bone quality. This whole set of determinants has to be taken into account and assessed if one intends to better understand and characterize bone “quality”. In that respect, further studies should be designed to characterize the molecular mechanisms involved in bone formation, repair, and remodeling. This Special Issue will be dedicated to “Molecular Mechanisms of Biomineralization in Healthy and Pathological Bone Tissues” with a focus on the mechanisms of bone formation and remodeling in both physiological and pathological conditions and the corresponding impact on bone quality. This Special Issue is intended to gather papers addressing various issues related to the assessment of bone quality in the fields of imaging, bioinformatics, cell differentiation, and regenerative medicine.

Dr. Emil Malucelli
Prof. Dr. David Bendahan
Guest Editors

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Keywords

  • New Approaches and Tools to Study Bone
  • 3D Cell Culture
  • Regenerative Medicine
  • Bioinformatics
  • Mesenchymal Stem Cell Differentiation
  • Bone Diseases
  • Imaging

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Published Papers (4 papers)

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Research

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16 pages, 4860 KiB  
Article
Calcite as a Precursor of Hydroxyapatite in the Early Biomineralization of Differentiating Human Bone-Marrow Mesenchymal Stem Cells
by Andrea Sorrentino, Emil Malucelli, Francesca Rossi, Concettina Cappadone, Giovanna Farruggia, Claudia Moscheni, Ana J. Perez-Berna, Jose Javier Conesa, Chiara Colletti, Norberto Roveri, Eva Pereiro and Stefano Iotti
Int. J. Mol. Sci. 2021, 22(9), 4939; https://doi.org/10.3390/ijms22094939 - 6 May 2021
Cited by 14 | Viewed by 2991
Abstract
Biomineralization is the process by which living organisms generate organized mineral crystals. In human cells, this phenomenon culminates with the formation of hydroxyapatite, which is a naturally occurring mineral form of calcium apatite. The mechanism that explains the genesis within the cell and [...] Read more.
Biomineralization is the process by which living organisms generate organized mineral crystals. In human cells, this phenomenon culminates with the formation of hydroxyapatite, which is a naturally occurring mineral form of calcium apatite. The mechanism that explains the genesis within the cell and the propagation of the mineral in the extracellular matrix still remains largely unexplained, and its characterization is highly controversial, especially in humans. In fact, up to now, biomineralization core knowledge has been provided by investigations on the advanced phases of this process. In this study, we characterize the contents of calcium depositions in human bone mesenchymal stem cells exposed to an osteogenic cocktail for 4 and 10 days using synchrotron-based cryo-soft-X-ray tomography and cryo-XANES microscopy. The reported results suggest crystalline calcite as a precursor of hydroxyapatite depositions within the cells in the biomineralization process. In particular, both calcite and hydroxyapatite were detected within the cell during the early phase of osteogenic differentiation. This striking finding may redefine most of the biomineralization models published so far, taking into account that they have been formulated using murine samples while studies in human cell lines are still scarce. Full article
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20 pages, 31275 KiB  
Article
Systemic Administration of G-CSF Accelerates Bone Regeneration and Modulates Mobilization of Progenitor Cells in a Rat Model of Distraction Osteogenesis
by Flavy Roseren, Martine Pithioux, Stéphane Robert, Laure Balasse, Benjamin Guillet, Edouard Lamy and Sandrine Roffino
Int. J. Mol. Sci. 2021, 22(7), 3505; https://doi.org/10.3390/ijms22073505 - 28 Mar 2021
Cited by 13 | Viewed by 3155
Abstract
Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), [...] Read more.
Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Histological analysis was performed and the number of circulating HSPCs, EPCs and MSCs was studied by flow cytometry. Contrary to control group, in the early phase of consolidation, a bony bridge with lower osteoclast activity and a trend of an increase in osteoblast activity were observed in the distracted callus in the G-CSF group, whereas, at the late phase of consolidation, a significantly lower neovascularization was observed. While no difference was observed in the number of circulating EPCs between control and G-CSF groups, the number of MSCs was significantly lower at the end of the latency phase and that of HSPCs was significantly higher 4 days after the bone lengthening. Our results indicate that G-CSF accelerates bone regeneration and modulates mobilization of progenitor cells during DO. Full article
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Review

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25 pages, 4456 KiB  
Review
Amelogenin-Derived Peptides in Bone Regeneration: A Systematic Review
by Antonino Fiorino, Alessandro Marturano, Giacomo Placella, Edoardo Staderini, Lorena Igual Domingo, Giuliano G. Cerulli, Roberto Tiribuzi and Paolo Blasi
Int. J. Mol. Sci. 2021, 22(17), 9224; https://doi.org/10.3390/ijms22179224 - 26 Aug 2021
Cited by 10 | Viewed by 4253
Abstract
Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived peptides, named LRAP, TRAP, SP, and C11, in bone tissue engineering. Interestingly, these peptides seem to maintain or even improve the [...] Read more.
Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived peptides, named LRAP, TRAP, SP, and C11, in bone tissue engineering. Interestingly, these peptides seem to maintain or even improve the biological activity of the full-length protein, which has received attention in the field of bone regeneration. In this article, the authors combined a systematic and a narrative review. The former is focused on the existing scientific evidence on LRAP, TRAP, SP, and C11’s ability to induce the production of mineralized extracellular matrix, while the latter is concentrated on the structure and function of amelogenin and amelogenin-derived peptides. Overall, the collected data suggest that LRAP and SP are able to induce stromal stem cell differentiation towards osteoblastic phenotypes; specifically, SP seems to be more reliable in bone regenerative approaches due to its osteoinduction and the absence of immunogenicity. However, even if some evidence is convincing, the limited number of studies and the scarcity of in vivo studies force us to wait for further investigations before drawing a solid final statement on the real potential of amelogenin-derived peptides in bone tissue engineering. Full article
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27 pages, 1354 KiB  
Review
Survey of MRI Usefulness for the Clinical Assessment of Bone Microstructure
by Enrico Soldati, Francesca Rossi, Jerome Vicente, Daphne Guenoun, Martine Pithioux, Stefano Iotti, Emil Malucelli and David Bendahan
Int. J. Mol. Sci. 2021, 22(5), 2509; https://doi.org/10.3390/ijms22052509 - 2 Mar 2021
Cited by 20 | Viewed by 4209
Abstract
Bone microarchitecture has been shown to provide useful information regarding the evaluation of skeleton quality with an added value to areal bone mineral density, which can be used for the diagnosis of several bone diseases. Bone mineral density estimated from dual-energy X-ray absorptiometry [...] Read more.
Bone microarchitecture has been shown to provide useful information regarding the evaluation of skeleton quality with an added value to areal bone mineral density, which can be used for the diagnosis of several bone diseases. Bone mineral density estimated from dual-energy X-ray absorptiometry (DXA) has shown to be a limited tool to identify patients’ risk stratification and therapy delivery. Magnetic resonance imaging (MRI) has been proposed as another technique to assess bone quality and fracture risk by evaluating the bone structure and microarchitecture. To date, MRI is the only completely non-invasive and non-ionizing imaging modality that can assess both cortical and trabecular bone in vivo. In this review article, we reported a survey regarding the clinically relevant information MRI could provide for the assessment of the inner trabecular morphology of different bone segments. The last section will be devoted to the upcoming MRI applications (MR spectroscopy and chemical shift encoding MRI, solid state MRI and quantitative susceptibility mapping), which could provide additional biomarkers for the assessment of bone microarchitecture. Full article
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