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Journal of Inorganic Biochemistry Jan 2021The extremely high levels of citrate in bone highlight its important role, which must be involved in some essential functional or structural role that is required for...
The extremely high levels of citrate in bone highlight its important role, which must be involved in some essential functional or structural role that is required for the development and maintenance of normal bone. However, biomineralization researches have emphasized the interaction between the citrate and inorganic minerals during crystallization in cell-free systems. It is difficult to obtain a thorough and comprehensive understanding from cell-free experimental conditions and treatment methods. In this study, by proposing an osteoblast mineralization experimental model, we explored the regulation of citrate on bone apatite crystal structure. Our studies show that citrate stabilizes two precursors and then inhibits their transformation into hydroxyapatite. Concomitantly, the smaller size and lower crystallinity mineral deposition emerge during citrate-mediated osteogenic mineralization. These findings may provide a new perspective for the mechanism of osteogenic mineralization and a basis for further understanding of bone metabolism.
Topics: Animals; Calcification, Physiologic; Cell Differentiation; Cell Line; Citric Acid; Extracellular Matrix; Mice; Osteoblasts
PubMed: 33129127
DOI: 10.1016/j.jinorgbio.2020.111269 -
Journal of Endodontics Mar 2018Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride (CPP-ACFP) have been shown to provide bioavailable ions to promote mineralization....
INTRODUCTION
Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride (CPP-ACFP) have been shown to provide bioavailable ions to promote mineralization. Hence, the aim of this study was to evaluate the materials' biocompatibility and osteogenic/calcification potential for endodontic applications.
METHODS
Human and mouse osteoblast-like and fibroblast-like cell lines were incubated with 0.05%-3.0% w/v CPP-ACP and CPP-ACFP, and toxicity, proliferation, alkaline phosphatase, interleukin (IL)-1α, and IL-6 production, collagen type I, osteocalcin, and osteopontin production, and mineralization/calcification were determined.
RESULTS
CPP-ACP and CPP-ACFP were non-toxic and had no significant effect on proliferation or production of the inflammatory cytokine IL-1α. Alkaline phosphatase activity of the osteoblast-like cells was significantly increased (P < .05) by CPP-ACP and CPP-ACFP, as was the production of the osteotropic cytokine IL-6, the formation of calcium mineral deposits, and the secretion of mineralization-related proteins (collagen type I and osteocalcin).
CONCLUSIONS
CPP-ACP and CPP-ACFP are biocompatible and have the potential to induce osteoblastic differentiation and mineralization. Potential applications include apexification, perforation repair, vital pulp therapy, and regenerative endodontic procedures.
Topics: Animals; Apatites; Biocompatible Materials; Calcification, Physiologic; Caseins; Cells, Cultured; Humans; Mice; Osteoblasts; Osteogenesis
PubMed: 29275851
DOI: 10.1016/j.joen.2017.11.005 -
Bone Nov 2019Acceleration of remodeling activity after menopause leads to bone loss and fragility, however, whether this is associated with modifications of bone matrix quality has...
Acceleration of remodeling activity after menopause leads to bone loss and fragility, however, whether this is associated with modifications of bone matrix quality has been less studied. The impact of variation in bone remodeling rate on bone matrix has been studied mainly in pathologies or anti-osteoporotic treatments. However, in healthy women this has been less studied. We analyzed, at the global level, bone matrix quality in bone biopsies from 3 groups of healthy women (20 per group): 1) before menopause (PreM), 2) 1 year after menopause (PostM, paired biopsies with preM), and 3) 14 (±9) years after menopause (LT-PostM). The mean degree of mineralization (DMB) and heterogeneity index (HI) of mineralization were assessed by X-ray microradiography on whole bone matrix; intrinsic properties (mineral/organic ratio, mineral maturity, mineral crystallinity, collagen maturity) were assessed by Fourier Transform Infrared microspectroscopy, microhardness by microindentation, both at a global level and calculated by mean of several measurements over the whole tissue area. In PostM compared to PreM (bone remodeling rate had doubled), mean DMB measured on the entire bone plane (whole bone matrix) of the sample was not different. HI was increased in trabecular bone indicating a higher heterogeneity of mineralization. However, in PostM, mineral/organic ratio (trabecular) and microhardness (cortical and trabecular) were decreased, whereas mineral/collagen maturation or crystal size/perfection were unchanged. Thus, in PostM, the local mineral content and microhardness were first affected. In LT-PostM (bone remodeling rate was 3 times higher), the mean DMB was still not different. However, the mineral/organic ratio, microhardness, mineral maturity, crystallinity all were lower compared to PreM and PostM, in both cortical and trabecular bone. Bone remodeling rate was negatively correlated with microhardness, DMB, mineral/organic and crystallinity. This suggests that increases in bone remodeling rates after menopause have a direct impact on bone quality by inducing the formation of more extensive "immature" bone areas, but the amount of immature bone does not cause modification of the global DMB.
Topics: Aged; Bone Density; Bone Matrix; Bone Remodeling; Calcification, Physiologic; Female; Humans; Menopause; Middle Aged; Spectroscopy, Fourier Transform Infrared; Women's Health
PubMed: 31404670
DOI: 10.1016/j.bone.2019.08.003 -
Biological Trace Element Research May 2022This study was designed to determine the effects of dietary hazelnut oil (HO) and sunflower oil (SO) on the mineral composition of chicken femur and tibia bones. A...
This study was designed to determine the effects of dietary hazelnut oil (HO) and sunflower oil (SO) on the mineral composition of chicken femur and tibia bones. A 40-day trial was initiated with 600 1-day-old Ross 308 chickens. Initially, the chickens were randomly divided into four main groups of 150 each according to the proportion of SO and HO supplementation in their diets: control SO (25 g/kg SO), LHO (25 g/kg HO), HHO (50 g/kg HO), and MO (50 g/kg blend of 25 g/kg SO + 25 g/kg HO). Each group was further divided into six subgroups of 25 chickens. At the end of the trial, four chickens from each of the six subgroups were randomly selected and slaughtered. Their right tibia and right femur bones were isolated and analyzed for macro (Ca, P, Mg) and trace (Fe, Cu, Mn, Zn, Cr, Co, and Se) minerals in addition to ether extract and ash. The results suggest that the diets' fat concentration and fatty acid composition significantly affected the Ca, P, Mg, Fe, Cu, Cr, and Se composition of tibia bones (p < 0.01). The ether extract and ash contents of the femur bones were increased in both HHO and MO groups (p < 0.05), while Fe and Cr compositions were lower in all femur bones, except those from SO chickens (p < 0.05). The Se content of femur bones in the LHO group was higher than the other treatment groups (p < 0.05). In conclusion, the amount of oil and fatty acid in the diet affected the accumulation of Ca, P, Mg, Fe, Cu, and Cr minerals in the tibia bone. Moreover, the amount of Cr and Fe was lower in the femur and tibia bones in the group that received the HO supplement and all groups in which the amount of oil fed was increased.
Topics: Animal Feed; Animals; Calcification, Physiologic; Chickens; Diet; Dietary Fats, Unsaturated; Dietary Supplements; Ether; Fatty Acids; Minerals; Plant Extracts
PubMed: 34278547
DOI: 10.1007/s12011-021-02833-9 -
Connective Tissue Research Aug 2014Bone's mineral properties, such as particle thickness and degree of alignment have been associated with bone quality. Bone formation, remodeling, aging of the tissue and...
Bone's mineral properties, such as particle thickness and degree of alignment have been associated with bone quality. Bone formation, remodeling, aging of the tissue and mineral homeostasis influence mineral particle properties leading to specific patterns across bone. Scanning small angle X-ray scattering (sSAXS) with synchrotron radiation is a powerful tool, which allows us to study bone's nanoscale mineral properties in a position-resolved way. We used sSAXS, fluorescence light microscopy and backscattered electron (BSE) imaging to study bone's mineral properties at the tibial midshaft of in vivo-loaded mice. By combining these techniques, we could detect local changes in mineral properties. Regions labeled with calcein fluorochrome have lower mean mineral thickness and degree of mineral alignment. We also observed thinner and less aligned mineral particles near blood vessels. We conclude that mineral properties (i) are altered by fluorochrome labeling and (ii) depend on the proximity to blood vessels.
Topics: Aging; Animals; Bone and Bones; Calcification, Physiologic; Female; Fluoresceins; Mice, Inbred C57BL; Nanostructures; X-Ray Diffraction
PubMed: 25158172
DOI: 10.3109/03008207.2014.923869 -
Bone Apr 2020Tissue-nonspecific alkaline phosphatase (TNAP) is necessary for skeletal mineralization by its ability to hydrolyze the mineralization inhibitor inorganic pyrophosphate...
Tissue-nonspecific alkaline phosphatase (TNAP) is necessary for skeletal mineralization by its ability to hydrolyze the mineralization inhibitor inorganic pyrophosphate (PP), which is mainly generated from extracellular ATP by ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Since children with TNAP deficiency develop bone metaphyseal auto-inflammations in addition to rickets, we hypothesized that TNAP also exerts anti-inflammatory effects relying on the hydrolysis of pro-inflammatory adenosine nucleotides into the anti-inflammatory adenosine. We explored this hypothesis in bone metaphyses of 7-day-old Alpl mice (encoding TNAP), in mineralizing hypertrophic chondrocytes and osteoblasts, and non-mineralizing mesenchymal stem cells (MSCs) and neutrophils, which express TNAP and are present, or can be recruited in the metaphysis. Bone metaphyses of 7-day-old Alpl mice had significantly increased levels of Il-1β and Il-6 and decreased levels of the anti-inflammatory Il-10 cytokine as compared with Alpl mice. In bone metaphyses, murine hypertrophic chondrocytes and osteoblasts, Alpl mRNA levels were much higher than those of the adenosine nucleotidases Npp1, Cd39 and Cd73. In hypertrophic chondrocytes, inhibition of TNAP with 25 μM of MLS-0038949 decreased the hydrolysis of AMP and ATP. However, TNAP inhibition did not significantly modulate ATP- and adenosine-associated effects in these cells. We observed that part of TNAP proteins in hypertrophic chondrocytes was sent from the cell membrane to matrix vesicles, which may explain why TNAP participated in the hydrolysis of ATP but did not significantly modulate its autocrine pro-inflammatory effects. In MSCs, TNAP did not participate in ATP hydrolysis nor in secretion of inflammatory mediators. In contrast, in neutrophils, TNAP inhibition with MLS-0038949 significantly exacerbated ATP-associated activation and secretion of IL-1β, and extended cell survival. Collectively, these results demonstrate that TNAP is a nucleotidase in both hypertrophic chondrocytes and neutrophils, and that this nucleotidase function is associated with autocrine effects on inflammation only in neutrophils.
Topics: Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Calcification, Physiologic; Mice; Nucleotidases; Osteoblasts
PubMed: 32028019
DOI: 10.1016/j.bone.2020.115262 -
BMC Molecular and Cell Biology Feb 2021The avian eggshell is a natural protective envelope that relies on the phenomenon of biomineralization for its formation. The shell is made of calcium carbonate in the... (Review)
Review
BACKGROUND
The avian eggshell is a natural protective envelope that relies on the phenomenon of biomineralization for its formation. The shell is made of calcium carbonate in the form of calcite, which contains hundreds of proteins that interact with the mineral phase controlling its formation and structural organization, and thus determine the mechanical properties of the mature biomaterial. We describe its mineralogy, structure and the regulatory interactions that integrate the mineral and organic constituents during eggshell biomineralization. Main Body. We underline recent evidence for vesicular transfer of amorphous calcium carbonate (ACC), as a new pathway to ensure the active and continuous supply of the ions necessary for shell mineralization. Currently more than 900 proteins and thousands of upregulated transcripts have been identified during chicken eggshell formation. Bioinformatic predictions address their functionality during the biomineralization process. In addition, we describe matrix protein quantification to understand their role during the key spatially- and temporally- regulated events of shell mineralization. Finally, we propose an updated scheme with a global scenario encompassing the mechanisms of avian eggshell mineralization.
CONCLUSION
With this large dataset at hand, it should now be possible to determine specific motifs, domains or proteins and peptide sequences that perform a critical function during avian eggshell biomineralization. The integration of this insight with genomic data (non-synonymous single nucleotide polymorphisms) and precise phenotyping (shell biomechanical parameters) on pure selected lines will lead to consistently better-quality eggshell characteristics for improved food safety. This information will also address the question of how the evolutionary-optimized chicken eggshell matrix proteins affect and regulate calcium carbonate mineralization as a good example of biomimetic and bio-inspired material design.
Topics: Animals; Avian Proteins; Biomineralization; Calcification, Physiologic; Calcium Carbonate; Chickens; Egg Proteins; Egg Shell; Female; Minerals
PubMed: 33579194
DOI: 10.1186/s12860-021-00350-0 -
Journal of Structural Biology Nov 2020In bone, structural components such as mineral extend across length scales to provide essential biomechanical functions. Using X-ray micro-computed tomography (µCT),...
In bone, structural components such as mineral extend across length scales to provide essential biomechanical functions. Using X-ray micro-computed tomography (µCT), and focused ion beam scanning electron microscopy (FIB-SEM) in serial-surface-view mode, together with 3D reconstruction, entire mouse skeletons and small bone tissue volumes were examined in normal wildtype (WT) and mutant Hyp mice (an animal model for X-linked hypophosphatemia/XLH, a disease with severe hypomineralization of bone). 3D thickness maps of the skeletons showed pronounced irregular thickening and abnormalities of many skeletal elements in Hyp mice compared to WT mice. At the micro- and nanoscale, near the mineralization front in WT tibial bone volumes, mineralization foci grow as expanding prolate ellipsoids (tesselles) to abut and pack against one another to form a congruent and contiguous mineral tessellation pattern within collagen bundles that contributes to lamellar periodicity. In the osteomalacic Hyp mouse bone, mineralization foci form and begin initial ellipsoid growth within normally organized collagen assembly, but their growth trajectory aborts. Mineralization-inhibiting events in XLH/Hyp (low circulating serum phosphate, and increased matrix osteopontin) combine to result in decreased mineral ellipsoid tessellation - a defective mineral-packing organization that leaves discrete mineral volumes isolated in the extracellular matrix such that ellipsoid packing/tessellation is not achieved. Such a severely altered mineralization pattern invariably leads to abnormal compliance, other aberrant biomechanical properties, and altered remodeling of bone, all of which indubitably lead to macroscopic bone deformities and anomalous mechanical performance in XLH/Hyp. Also, we show the relationship of osteocytes and their cell processes to this mineralization pattern.
Topics: Animals; Calcification, Physiologic; Disease Models, Animal; Familial Hypophosphatemic Rickets; Male; Mice; Mice, Inbred C57BL; Microscopy; Minerals; Osteocytes; Osteopontin; Tibia; X-Ray Microtomography
PubMed: 32805412
DOI: 10.1016/j.jsb.2020.107603 -
Bone Apr 2019Certain avian tendons have been studied previously as a model system for normal mineralization of vertebrates in general. In this regard, the gastrocnemius tendon in the...
Certain avian tendons have been studied previously as a model system for normal mineralization of vertebrates in general. In this regard, the gastrocnemius tendon in the legs of turkeys mineralizes in a well defined temporal and spatial manner such that changes in the initial and subsequent events of mineral formation can be associated with time and specific locations in the tissue. In the present investigation, these parameters and mineral deposition have been correlated with the expression of several genes and the synthesis and secretion of their related extracellular matrix proteins by the composite tenocytes of the tendon. Quantitative polymerase chain reaction analysis demonstrates that mRNA expression of the non-collagenous genes of bone sialoprotein, osteopontin, and osteocalcin corresponds well with the temporal and spatial onset and progression of mineralization. Immunolocalization separately confirms the synthesis and secretion of these matrix molecules. The expression of other non-collagenous genes such as decorin does not show strong correlation with turkey leg tendon mineralization, and expression of vimentin, a cytoskeletal component which may be regulated by biomechanical factors in the tendon, may lead to inhibition of osteocalcin expression during the development and mineralization of the tissue. The overall results of this work provide insight into direct temporal and spatial relations between the genes and proteins of interest as well as the formation and deposition of mineral in the avian tendon model.
Topics: Animals; Avian Proteins; Birds; Calcification, Physiologic; Muscle, Skeletal; Polymerase Chain Reaction; Tendons
PubMed: 30419319
DOI: 10.1016/j.bone.2018.11.005 -
Macromolecular Bioscience Jan 2019Dentin phosphoprotein (DPP) is a major component of the dentin matrix playing crucial role in hydroxyapatite deposition during bone mineralization, making it a prime...
Dentin phosphoprotein (DPP) is a major component of the dentin matrix playing crucial role in hydroxyapatite deposition during bone mineralization, making it a prime candidate for the design of novel materials for bone and tooth regeneration. The bioactivity of DPP-derived proteins is controlled by the phosphorylation and dephosphorylation of the serine residues. Here an enzyme-responsive peptide nanofiber system inducing biomineralization is demonstrated. It closely emulates the structural and functional properties of DPP and facilitates apatite-like mineral deposition. The DPP-mimetic peptide molecules self-assemble through dephosphorylation by alkaline phosphatase (ALP), an enzyme participating in tooth and bone matrix mineralization. Nanofiber network formation is also induced through addition of calcium ions. The gelation process following nanofiber formation produces a mineralized extracellular matrix like material, where scaffold properties and phosphate groups promote mineralization. It is demonstrated that the DPP-mimetic peptide nanofiber networks can be used for apatite-like mineral deposition for bone regeneration.
Topics: Biomimetic Materials; Bone Regeneration; Calcification, Physiologic; Cell Line, Tumor; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Nanofibers; Peptides; Phosphoproteins; Sialoglycoproteins
PubMed: 29745025
DOI: 10.1002/mabi.201800080