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1.
Math Biosci Eng ; 21(4): 5138-5163, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38872530

ABSTRACT

The objective of the present study was to improve our understanding of the complex biological process of bone mineralization by performing mathematical modeling with the Caputo-Fabrizio fractional operator. To obtain a better understanding of Komarova's bone mineralization process, we have thoroughly examined the boundedness, existence, and uniqueness of solutions and stability analysis within this framework. To determine how model parameters affect the behavior of the system, sensitivity analysis was carried out. Furthermore, the fractional Adams-Bashforth method has been used to carry out numerical and graphical simulations. Our work is significant owing to its comparison of fractional- and integer-order models, which provides novel insight into the effectiveness of fractional operators in representing the complex dynamics of bone mineralization.


Subject(s)
Calcification, Physiologic , Computer Simulation , Models, Biological , Nonlinear Dynamics , Calcification, Physiologic/physiology , Humans , Algorithms , Bone and Bones/physiology , Animals , Computer Graphics
2.
J Extracell Vesicles ; 13(6): e12450, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38859730

ABSTRACT

Matrix vesicles (MVs) provide the initial site for amorphous hydroxyapatite (HA) formation within mineralizing osteoblasts. Although Na+/Ca2+ exchanger isoform-3 (NCX3, SLC8A3) was presumed to function as major Ca2+ transporter responsible for Ca2+ extrusion out of osteoblast into the calcifying bone matrix, its presence and functional role in MVs have not been investigated. In this study, we investigated the involvement of NCX3 in MV-mediated mineralization process and its impact on bone formation. Using differentiated MC3T3-E1 cells, we demonstrated that NCX3 knockout in these cells resulted in a significant reduction of Ca2+ deposition due to reduced Ca2+ entry within the MVs, leading to impaired mineralization. Consequently, the capacity of MVs to promote extracellular HA formation was diminished. Moreover, primary osteoblast isolated from NCX3 deficient mice (NCX3-/-) exhibits reduced mineralization efficacy without any effect on osteoclast activity. To validate this in vitro finding, µCT analysis revealed a substantial decrease in trabecular bone mineral density in both genders of NCX3-/- mice, thus supporting the critical role of NCX3 in facilitating Ca2+ uptake into the MVs to initiate osteoblast-mediated mineralization. NCX3 expression was also found to be the target of downregulation by inflammatory mediators in vitro and in vivo. This newfound understanding of NCX3's functional role in MVs opens new avenues for therapeutic interventions aimed at enhancing bone mineralization and treating mineralization-related disorders.


Subject(s)
Calcification, Physiologic , Calcium , Mice, Knockout , Osteoblasts , Sodium-Calcium Exchanger , Animals , Osteoblasts/metabolism , Sodium-Calcium Exchanger/metabolism , Mice , Calcium/metabolism , Male , Osteogenesis , Cell Differentiation , Female , Extracellular Vesicles/metabolism , Cell Line
3.
Glob Chang Biol ; 30(6): e17371, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38863267

ABSTRACT

As the balance between erosional and constructive processes on coral reefs tilts in favor of framework loss under human-induced local and global change, many reef habitats worldwide degrade and flatten. The resultant generation of coral rubble and the beds they form can have lasting effects on reef communities and structural complexity, threatening the continuity of reef ecological functions and the services they provide. To comprehensively capture changing framework processes and predict their evolution in the context of climate change, heavily colonized rubble fragments were exposed to ocean acidification (OA) conditions for 55 days. Controlled diurnal pH oscillations were incorporated in the treatments to account for the known impact of diel carbonate chemistry fluctuations on calcification and dissolution response to OA. Scenarios included contemporary pH (8.05 ± 0.025 diel fluctuation), elevated OA (7.90 ± 0.025), and high OA (7.70 ± 0.025). We used a multifaceted approach, combining chemical flux analyses, mass alteration measurements, and computed tomography scanning images to measure total and chemical bioerosion, as well as chemically driven secondary calcification. Rates of net carbonate loss measured in the contemporary conditions (1.36 kg m-2 year-1) were high compared to literature and increased in OA scenarios (elevated: 1.84 kg m-2 year-1 and high: 1.59 kg m-2 year-1). The acceleration of these rates was driven by enhanced chemical dissolution and reduced secondary calcification. Further analysis revealed that the extent of these changes was contingent on the density of the coral skeleton, in which the micro- and macroborer communities reside. Findings indicated that increased mechanical bioerosion rates occurred in rubble with lower skeletal density, which is of note considering that corals form lower-density skeletons under OA. These direct and indirect effects of OA on chemical and mechanical framework-altering processes will influence the permanence of this crucial habitat, carrying implications for biodiversity and reef ecosystem function.


Subject(s)
Anthozoa , Climate Change , Coral Reefs , Seawater , Anthozoa/physiology , Anthozoa/chemistry , Animals , Seawater/chemistry , Hydrogen-Ion Concentration , Calcification, Physiologic , Carbonates/chemistry , Carbonates/analysis , Oceans and Seas , Ocean Acidification
4.
Biomed Mater ; 19(4)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38815596

ABSTRACT

As the structural basis of connective and load-bearing tissues, collagen fibers with orientation play an important role in the mechanical properties and physiological and biochemical functions of the tissues, but viable methods for preparing scaffolds with highly oriented collagenous structure still need to be further studied. In this study, pure collagen was used as printing ink to 3D printing. Harnessing oriented collagen fiber structure by 3D printing for promoting mechanical and osteogenic properties of scaffolds. The scaffolds with different printed angles and thicknesses were prepared to fit the bone defect site and realize personalized customization. The orientation assembly of collagen fibers was promoted by shear force action of 3D printing, the regular arrangement of collagen fibers and stabilization of fiber structure were promoted by pH adjustment and glutaraldehyde cross-linking, and the collagen fibers were mineralized by cyclic mineralization method. The microscopic morphology of fiber arrangement in the scaffolds were investigated by scanning electron microscopy. Results demonstrated that collagen fibers were changed from non-oriented to oriented after 3D printing. And the tensile modulus of the scaffolds with oriented collagen fibers was nine times higher than that of the scaffolds with non-oriented fibers. Moreover, the effects of oriented collagen fibers on the proliferation, differentiation and mineralization of MC3T3-E1 cells were studied by CCK-8 assay, live/dead cell staining, alkaline phosphatase activity test, and Alizarin red staining. The results indicated that cell proliferation, differentiation and mineralization were significantly promoted by oriented collagen fibers, and the cells proliferated directionally in the direction of the fibers. Taken together, mineralized collagen fiber scaffolds with oriented collagen fibers have great potential in bone tissue engineering applications.


Subject(s)
Cell Differentiation , Cell Proliferation , Collagen , Osteoblasts , Osteogenesis , Printing, Three-Dimensional , Tissue Engineering , Tissue Scaffolds , Tissue Scaffolds/chemistry , Mice , Animals , Collagen/chemistry , Tissue Engineering/methods , Osteoblasts/cytology , Materials Testing , Tensile Strength , Biocompatible Materials/chemistry , Cell Line , Microscopy, Electron, Scanning , Calcification, Physiologic , 3T3 Cells , Stress, Mechanical
5.
Biomed Mater ; 19(4)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38815600

ABSTRACT

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 µM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.


Subject(s)
Biflavonoids , Catechin , Cell Survival , Hydrogen Peroxide , Magnesium Oxide , Nanoparticles , Osteoblasts , Osteogenesis , Oxidative Stress , Proanthocyanidins , Reactive Oxygen Species , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/cytology , Proanthocyanidins/pharmacology , Proanthocyanidins/chemistry , Catechin/chemistry , Catechin/pharmacology , Oxidative Stress/drug effects , Magnesium Oxide/chemistry , Reactive Oxygen Species/metabolism , Animals , Cell Survival/drug effects , Biflavonoids/pharmacology , Biflavonoids/chemistry , Osteogenesis/drug effects , Hydrogen Peroxide/chemistry , Nanoparticles/chemistry , Delayed-Action Preparations/chemistry , Mice , Calcification, Physiologic/drug effects , Spectroscopy, Fourier Transform Infrared
6.
Calcif Tissue Int ; 115(1): 63-77, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38733411

ABSTRACT

Osteopontin (OPN) and Bone Sialoprotein (BSP), abundantly expressed by osteoblasts and osteoclasts, appear to have important, partly overlapping functions in bone. In gene-knockout (KO, -/-) models of either protein and their double (D)KO in the same CD1/129sv genetic background, we analyzed the morphology, matrix characteristics, and biomechanical properties of femur bone in 2 and 4 month old, male and female mice. OPN-/- mice display inconsistent, perhaps localized hypermineralization, while the BSP-/- are hypomineralized throughout ages and sexes, and the low mineralization of young DKO mice recovers with age. The higher contribution of primary bone remnants in OPN-/- shafts suggests a slow turnover, while their lower percentage in BSP-/- indicates rapid remodeling, despite FTIR-based evidence in this genotype of a high maturity of the mineralized matrix. In 3-point bending assays, OPN-/- bones consistently display higher Maximal Load, Work to Max. Load and in young mice Ultimate Stress, an intrinsic characteristic of the matrix. Young male and old female BSP-/- also display high Work to Max. Load along with low Ultimate Stress. Principal Component Analysis confirms the major role of morphological traits in mechanical competence, and evidences a grouping of the WT phenotype with the OPN-/- and of BSP-/- with DKO, driven by both structural and matrix parameters, suggesting that the presence or absence of BSP has the most profound effects on skeletal properties. Single or double gene KO of OPN and BSP thus have multiple distinct effects on skeletal phenotypes, confirming their importance in bone biology and their interplay in its regulation.


Subject(s)
Integrin-Binding Sialoprotein , Mice, Knockout , Osteopontin , Animals , Osteopontin/genetics , Osteopontin/metabolism , Female , Male , Mice , Integrin-Binding Sialoprotein/genetics , Integrin-Binding Sialoprotein/metabolism , Biomechanical Phenomena , Bone and Bones/metabolism , Bone Density/physiology , Bone Density/genetics , Femur/metabolism , Calcification, Physiologic/physiology , Calcification, Physiologic/genetics
7.
Bone ; 185: 117126, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38777312

ABSTRACT

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human-equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels, and prevented mineralization defects. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function, besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects on bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes.


Subject(s)
Bone and Bones , Calcimimetic Agents , Hyperparathyroidism, Secondary , Peptides , Rats, Sprague-Dawley , Renal Insufficiency, Chronic , Animals , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/pathology , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/metabolism , Bone and Bones/drug effects , Bone and Bones/metabolism , Bone and Bones/pathology , Peptides/pharmacology , Calcimimetic Agents/pharmacology , Calcimimetic Agents/therapeutic use , Rats , Parathyroid Hormone/pharmacology , Male , Calcification, Physiologic/drug effects , Bone Density/drug effects
8.
Food Chem Toxicol ; 189: 114772, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38821392

ABSTRACT

Exposure to plastic-derived estrogen-mimicking endocrine-disrupting bisphenols can have a long-lasting effect on bone health. However, gestational exposure to bisphenol A (BPA) and its analogue, bisphenol S (BPS), on offspring's bone mineralization is unclear. The effects of in-utero bisphenol exposure were examined on the offspring's bone parameters. BPA and BPS (0.0, 0.4 µg/kg bw) were administered to pregnant Wistar rats via oral gavage from gestational day 4-21. Maternal exposure to BPA and BPS increased bone mineral content and density in the offspring aged 30 and 90 days (P < 0.05). Plasma analysis revealed that alkaline phosphatase, and Gla-type osteocalcin were significantly elevated in the BPS-exposed offspring (P < 0.05). The expression of BMP1, BMP4, and their signaling mediators SMAD1 mRNAs were decreased in BPS-exposed osteoblast SaOS-2 cells (P < 0.05). The expression of extracellular matrix proteins such as ALPL, COL1A1, DMP1, and FN1 were downregulated (P < 0.05). Bisphenol co-incubation with noggin decreased TGF-ß1 expression, indicating its involvement in bone mineralization. Altered mineralization could be due to dysregulated expression of bone morphogenetic proteins and signalling mediators in the osteoblast cells. Thus, bisphenol exposure during gestation altered growth and bone mineralization in the offspring, possibly by modulating the expression of Smad-dependent BMP/TGF-ß1 signalling mediators.


Subject(s)
Benzhydryl Compounds , Calcification, Physiologic , Phenols , Prenatal Exposure Delayed Effects , Rats, Wistar , Sulfones , Animals , Phenols/toxicity , Benzhydryl Compounds/toxicity , Female , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Calcification, Physiologic/drug effects , Rats , Sulfones/toxicity , Humans , Smad1 Protein/metabolism , Smad1 Protein/genetics , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/blood , Maternal Exposure/adverse effects , Bone Morphogenetic Protein 4/metabolism , Bone Morphogenetic Protein 4/genetics , Osteocalcin/metabolism , Osteocalcin/genetics , Bone Morphogenetic Protein 1/metabolism , Bone Morphogenetic Protein 1/genetics , Male , Osteoblasts/drug effects , Osteoblasts/metabolism , Bone Density/drug effects , Endocrine Disruptors/toxicity , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Carrier Proteins
9.
Bone ; 185: 117112, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38697384

ABSTRACT

This review examines the possible role of mitochondria in maintaining calcium and phosphate ion homeostasis and participating in the mineralization of bone, cartilage and other vertebrate hard tissues. The paper builds on the known structural features of mitochondria and the documented observations in these tissues that the organelles contain calcium phosphate granules. Such deposits in mitochondria putatively form to buffer excessively high cytosolic calcium ion concentrations and prevent metabolic deficits and even cell death. While mitochondria protect cytosolic enzyme systems through this buffering capacity, the accumulation of calcium ions by mitochondria promotes the activity of enzymes of the tricarboxylic acid (TCA/Krebs) cycle, increases oxidative phosphorylation and ATP synthesis, and leads to changes in intramitochondrial pH. These pH alterations influence ion solubility and possibly the transitions and composition in the mineral phase structure of the granules. Based on these considerations, mitochondria are proposed to support the mineralization process by providing a mobile store of calcium and phosphate ions, in smaller cluster or larger granule form, while maintaining critical cellular activities. The rise in the mitochondrial calcium level also increases the generation of citrate and other TCA cycle intermediates that contribute to cell function and the development of extracellular mineral. This paper suggests that another key role of the mitochondrion, along with the effects just noted, is to supply phosphate ions, derived from the breakdown of ATP, to endolysosomes and autophagic vesicles originating in the endoplasmic reticulum and Golgi and at the plasma membrane. These many separate but interdependent mitochondrial functions emphasize the critical importance of this organelle in the cellular control of vertebrate mineralization.


Subject(s)
Calcification, Physiologic , Mitochondria , Vertebrates , Animals , Mitochondria/metabolism , Humans , Calcification, Physiologic/physiology , Vertebrates/metabolism , Calcium/metabolism , Phosphates/metabolism
10.
Int J Mol Sci ; 25(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731947

ABSTRACT

Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17ß-estradiol (E2) in the matrix mineralization of MC3T3-E1, an osteoblast-like cell line. In the culture media-containing stripped serum, in which small lipophilic molecules such as steroid hormones including E2 were depleted, matrix mineralization was significantly reduced. However, the E2 treatment induced this. The E2 effects were suppressed by ICI182,780, the estrogen receptor (ER)α, and the ERß antagonist, as well as their mRNA knockdown, whereas Raloxifene, an inhibitor of estrogen-induced transcription, and G15, a G-protein-coupled estrogen receptor (GPER) 1 inhibitor, had little or no effect. Furthermore, the E2-activated matrix mineralization was disrupted by PMA, a PKC activator, and SB202190, a p38 MAPK inhibitor, but not by wortmannin, a PI3K inhibitor. Matrix mineralization was also induced by the culture media from the E2-stimulated cell culture. This effect was hindered by PMA or heat treatment, but not by SB202190. These results indicate that E2 activates the p38 MAPK pathway via ERs independently from actions in the nucleus. Such activation may cause the secretion of certain signaling molecule(s), which inhibit the PKC pathway. Our study provides a novel pathway of E2 action that could be a therapeutic target to activate matrix mineralization under various diseases, including osteoporosis.


Subject(s)
Estradiol , Osteoblasts , Signal Transduction , Animals , Mice , Estradiol/pharmacology , Osteoblasts/metabolism , Osteoblasts/drug effects , Signal Transduction/drug effects , Calcification, Physiologic/drug effects , Cell Line , p38 Mitogen-Activated Protein Kinases/metabolism , Receptors, Estrogen/metabolism , Receptors, Estrogen/genetics , Estrogens/pharmacology , Estrogens/metabolism , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/genetics
11.
Sci Rep ; 14(1): 11121, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750108

ABSTRACT

The chemical and isotopic composition of stony coral skeletons form an important archive of past climate. However, these reconstructions are largely based on empirical relationships often complicated by "vital effects" arising from uncertain physiological processes of the coral holobiont. The skeletons of deep-sea corals, such as Desmophyllum dianthus, are characterised by micron-scale or larger geochemical heterogeneity associated with: (1) centres of calcification (COCs) where nucleation of new skeleton begins, and (2) fibres that thicken the skeleton. These features are difficult to sample cleanly using traditional techniques, resulting in uncertainty surrounding both the causes of geochemical differences and their influence on environmental signals. Here we combine optical, and in-situ chemical and isotopic, imaging tools across a range of spatial resolutions (~ 100 nm to 10 s of µm) in a correlative multimodal imaging (CMI) approach to isolate the microstructural geochemistry of each component. This reveals COCs are characterised by higher organic content, Mg, Li and Sr and lower U, B and δ11B compared to fibres, reflecting the contrasting biomineralisation mechanisms employed to construct each feature. CMI is rarely applied in Environmental/Earth Sciences, but here we illustrate the power of this approach to unpick the "vital effects" in D. dianthus, and by extension, other scleractinian corals.


Subject(s)
Anthozoa , Anthozoa/metabolism , Animals , Calcification, Physiologic , Biomineralization
12.
Int. j. cardiovasc. sci. (Impr.) ; 37(suppl.1): 98-98, abr. 2024. ilus
Article in Portuguese | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1538354

ABSTRACT

INTRODUÇÃO: Várias etiologias podem levar à inflamação pericárdica, sendo as mais frequentes a tuberculosa e viral. O pericárdio inflamado e também o processo reparativo incluindo fibrose e espessamento subsequente estão relacionados a quadros de constricção e insuficiência cardíaca. Descrevemos um caso em que a etiologia da pericardite constrictiva (PC) foi incomum, secundária à trauma do coração. CASO CLÍNICO: Homem, 69 anos, trabalhador rural, ex-tabagista, sem outras comorbidades. Há 3 meses passou a apresentar dispneia aos moderados esforços e edema de membro inferiores. À avaliação, apresentava sinais de congestão sistêmica, como turgência jugular e ascite, além de pulso paradoxal e sinal de kussmaul. Negou febre, perda de peso, sudorese noturna ou uso de medicações. Em radiografia de tórax, evidenciou-se radiopacidade em silhueta cardíaca sugestiva de calcificação. Ecocardiograma transtorácico evidenciou trombo em átrio direito e pericárdio espesso, associado à imagem hiperrefringrente sugestiva de "massa" com sinais de compressão extrínseca do ventrículo direito e rechaçamento em direção ao ventrículo esquerdo (VE), com retificação do septo interventricular e diminuição da cavidade do VE, resultando em uma disfunção diastólica acentuada, mantendo função sistólica biventricular preservada. Realizado estudo tomográfico, que confirmou intensa calcificação pericárdica com imagem de "pseudotumor" de contornos irregulares, gerando intensa constricção e confirmando o diagnóstico de PC. Paciente foi submetido à pericardiectomia, que evidenciou grande quantidade de trombo calcificado no interior do "pseudo-tumor", com posterior resolução do quadro clínico. Após excluir múltiplas etiologias de pericardite e revisar história clínica, paciente relatou trauma torácico contundente por cabeçada bovina há cerca de 10 anos, que cursou com dor torácica e dispneia por meses, sem atendimento médico na ocasião, sendo a provável etiologia do quadro. CONCLUSÃO: A pericardite constrictiva, diagnóstico infrequente, está ligada a elevada morbimortalidade e pode ser secundária a qualquer comprometimento pericárdico, incluindo trauma torácico. Portanto, faz-se necessário diagnosticar e tratar situações que podem cursar com pericardite aguda e, possivelmente, com PC.


Subject(s)
Humans , Male , Aged , Pericarditis, Constrictive , Calcification, Physiologic , Heart Failure
13.
Mar Biotechnol (NY) ; 26(3): 539-549, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38652191

ABSTRACT

Many organisms incorporate inorganic solids into their tissues to improve functional and mechanical properties. The resulting mineralized tissues are called biominerals. Several studies have shown that nacreous biominerals induce osteoblastic extracellular mineralization. Among them, Pinctada margaritifera is well known for the ability of its organic matrix to stimulate bone cells. In this context, we aimed to study the effects of shell extracts from three other Pinctada species (Pinctada radiata, Pinctada maxima, and Pinctada fucata) on osteoblastic extracellular matrix mineralization, by using an in vitro model of mouse osteoblastic precursor cells (MC3T3-E1). For a better understanding of the Pinctada-bone mineralization relationship, we evaluated the effects of 4 other nacreous mollusks that are phylogenetically distant and distinct from the Pinctada genus. In addition, we tested 12 non-nacreous mollusks and one extra-group. Biomineral shell powders were prepared, and their organic matrix was partially extracted using ethanol. Firstly, the effect of these powders and extracts was assessed on the viability of MC3T3-E1. Our results indicated that neither the powder nor the ethanol-soluble matrix (ESM) affected cell viability at low concentrations. Then, we evaluated osteoblastic mineralization using Alizarin Red staining and we found a prominent MC3T3-E1 mineralization mainly induced by nacreous biominerals, especially those belonging to the Pinctada genus. However, few non-nacreous biominerals were also able to stimulate the extracellular mineralization. Overall, our findings validate the remarkable ability of CaCO3 biomineral extracts to promote bone mineralization. Nevertheless, further in vitro and in vivo studies are needed to uncover the mechanisms of action of biominerals in bone.


Subject(s)
Animal Shells , Calcification, Physiologic , Calcium Carbonate , Osteoblasts , Pinctada , Animals , Mice , Osteoblasts/metabolism , Osteoblasts/drug effects , Pinctada/metabolism , Calcium Carbonate/metabolism , Calcium Carbonate/chemistry , Calcium Carbonate/pharmacology , Calcification, Physiologic/drug effects , Animal Shells/chemistry , Cell Survival/drug effects , Cell Line , Extracellular Matrix/metabolism , Nacre/metabolism , Biomineralization
14.
ACS Biomater Sci Eng ; 10(5): 2983-2994, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38634615

ABSTRACT

Calcified cartilage digested by chondroclasts provides an excellent scaffold to initiate bone formation. We analyzed bioactive proteins and microarchitecture of calcified cartilage either separately or in combination and evaluated biomimetic osteogenic culture conditions of surface-coated micropatterning. To do so, we prepared a crude extract from porcine femoral growth plates, which enhanced in vitro mineralization when coated on flat-bottom culture dishes, and identified four candidate proteins by fractionation and mass spectrometry. Murine homologues of two candidates, desmoglein 4 (DSG4) and peroxiredoxin 6 (PRDX6), significantly promoted osteogenic activity based on in vitro mineralization and osteoblast differentiation. Moreover, we observed DSG4 and PRDX6 protein expression in mouse femur. In addition, we designed circular, triangular, and honeycomb micropatterns with 30 or 50 µm units, either isolated or connected, to mimic hypertrophic chondrocyte-sized compartments. Isolated, larger honeycomb patterns particularly enhanced osteogenesis in vitro. Mineralization on micropatterns was positively correlated with the reduction of osteoblast migration distance in live cell imaging. Finally, we evaluated possible combinatorial effects of coat proteins and micropatterns and observed an additive effect of DSG4 or PRDX6 coating with micropatterns. These data suggest that combining a bioactive surface coating with osteogenic micropatterns may recapitulate initiation of bone formation during endochondral ossification.


Subject(s)
Osteogenesis , Animals , Osteogenesis/drug effects , Mice , Swine , Osteoblasts/metabolism , Osteoblasts/cytology , Osteoblasts/drug effects , Cell Differentiation/drug effects , Cartilage/metabolism , Cartilage/cytology , Peroxiredoxin VI/metabolism , Calcification, Physiologic/drug effects
15.
Bone ; 185: 117111, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38679220

ABSTRACT

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = -0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.


Subject(s)
Alcohol Drinking , Calcification, Physiologic , Cortical Bone , Macaca fascicularis , Animals , Male , Porosity , Alcohol Drinking/physiopathology , Cortical Bone/drug effects , Cortical Bone/pathology , Cortical Bone/diagnostic imaging , Calcification, Physiologic/drug effects , Biomechanical Phenomena/drug effects , X-Ray Microtomography , Tibia/drug effects , Tibia/diagnostic imaging , Tibia/pathology , Ethanol/pharmacology , Spectrum Analysis, Raman , Bone Density/drug effects
16.
Carbohydr Polym ; 335: 122063, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38616074

ABSTRACT

The surface properties of cardiovascular biomaterials play a critical role in their biological responses. Although bacterial nanocellulose (BNC) materials have exhibited potential applications in cardiovascular implants, the impact of their surface characteristics on biocompatibility has rarely been studied. This study investigated the mechanism for the biocompatibility induced by the physicochemical properties of both sides of BNC. With greater wettability and smoothness, the upper BNC surface reduced protein adsorption by 25 % compared with the lower surface. This prolonged the plasma re-calcification time by 14 % in venous blood. Further, compared with the lower BNC surface, the upper BNC surface prolonged the activated partial thromboplastin time by 5 % and 4 % in arterial and venous blood, respectively. Moreover, the lower BNC surface with lesser rigidity, higher roughness, and sparser fiber structure promoted cell adhesion. The lower BNC surface enhanced the proliferation rate of L929 and HUVECs cells by 15 % and 13 %, respectively, compared with the upper BNC surface. With lesser stiffness, the lower BNC surface upregulated the expressions of CD31 and eNOS while down-regulating the ICAM-1 expression - This promoted the proliferation of HUVECs. The findings of this study will provide valuable insights into the design of blood contact materials and cardiovascular implants.


Subject(s)
Biocompatible Materials , Body Fluids , Humans , Adsorption , Biocompatible Materials/pharmacology , Calcification, Physiologic , Human Umbilical Vein Endothelial Cells
17.
Animal ; 18(4): 101130, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38579665

ABSTRACT

To maximize the efficiency of dietary P utilization in swine production, understanding the mechanisms of P utilization in lactating sows is relevant due to their high P requirement and the resulting high inorganic P intake. Gaining a better knowledge of the Ca and P quantities that can be mobilized from bones during lactation, and subsequently replenished during the following gestation, would enable the development of more accurate P requirements incorporating this process of bone dynamics. The objective was to measure the amount of body mineral reserves mobilized during lactation, depending on dietary digestible P and phytase addition and to measure the amount recovered during the following gestation. Body composition of 24 primiparous sows was measured by dual-energy x-ray absorptiometry 2, 14, 26, 70 and 110 days after farrowing. Four lactation diets were formulated to cover nutritional requirements, with the exception of Ca and digestible P: 100% (Lact100; 9.9 g Ca and 3.0 g digestible P/kg), 75% (Lact75), 50% without added phytase (Lact50) and 50% with added phytase (Lact50 + FTU). The gestation diet was formulated to cover the nutritional requirements of Ca and digestible P (8.2 g Ca and 2.6 g digestible P/kg). During the 26 days of lactation, each sow mobilized body mineral reserves. The mean amount of mobilized bone mineral content (BMC) was 664 g, representing 240 g Ca and 113 g P. At weaning, the BMC (g/kg of BW) of Lact50 sows tended to be lower than Lact100 sows (-12.8%, linear Ca and P effect × quadratic time effect) while the BMC of Lact50 + FTU sows remained similar to that of Lact100 sows. During the following gestation, BMC returned to similar values among treatments. Therefore, the sows fed Lact50 could recover from the higher bone mineral mobilization that occurred during lactation. The P excretion was reduced by 40 and 43% in sows fed Lact50 and Lact50 + FTU, respectively, relative to sows fed Lact100. In conclusion, the quantified changes in body composition during the lactation and following gestation of primiparous sows show that bone mineral reserves were mobilized and recovered and that its degree was dependent on the dietary P content and from phytase supplementation during lactation. In the future, considering this potential of the sows' bone mineralization dynamics within the factorial assessment of P requirement and considering the digestible P equivalency of microbial phytase could greatly limit the dietary use of inorganic phosphates and, thus, reduce P excretion.


Subject(s)
6-Phytase , Phosphorus, Dietary , Female , Animals , Swine , Calcium , Lactation , Calcification, Physiologic , 6-Phytase/metabolism , Diet/veterinary , Calcium, Dietary , Minerals , Animal Feed/analysis , Phosphorus/metabolism
18.
Biochem Biophys Res Commun ; 710: 149854, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38581947

ABSTRACT

Peripheral serotonin levels are associated with cardiovascular disease risk. We previously found that serum serotonin levels are higher in hyperlipidemic mice than wild-type mice. Evidence also suggests that serotonin regulates biomineralization, in that serotonin treatment augments TNF-a-induced matrix calcification of aortic valve interstitial cells and that a selective inhibitor of peripheral serotonin, LP533401, rescues bone loss induced by ovariectomy in mice. Thus, in the present study, we examined the effects of LP533401 on both skeletal bone mineral density (BMD) and aortic calcification in both young and older hyperlipidemic mice susceptible to calcific atherosclerosis and bone loss. By serial in vivo microCT imaging, we assessed BMD and aortic calcification of Apoe-/- mice fed an atherogenic (high cholesterol) diet alone or mixed with LP533401. Results show that in the young mice, LP533401 blunted skeletal bone loss in lumbar vertebrae but not in femurs. LP533401 also blunted the initial development of aortic calcification but not its progression. Echocardiographic analysis showed that LP533401 blunted both hyperlipidemia-induced cardiac hypertrophy and left ventricular dysfunction. In the older mice, LP533401 increased the BMD of lumbar vertebrae but not of femurs. The aortic calcification progressed in both controls and LP533401-treated mice, but, at post-treatment, LP533401-treated mice had significantly less aortic calcification than the controls. These findings suggest that LP533401 mitigates adverse effects of hyperlipidemia on skeletal and vascular tissues in site- and stage-dependent manners.


Subject(s)
Atherosclerosis , Calcinosis , Hyperlipidemias , Pyrimidines , Vascular Calcification , Female , Mice , Animals , Serotonin , Calcification, Physiologic , Aortic Valve/diagnostic imaging , Hyperlipidemias/complications , Vascular Calcification/etiology
19.
PLoS One ; 19(4): e0301874, 2024.
Article in English | MEDLINE | ID: mdl-38630684

ABSTRACT

Mytilus edulis is a commercially and ecologically important species found along the east coast of the United States. Ecologically, M. edulis improves water quality through filtration feeding and provides habitat formation and coastal protection through reef formation. Like many marine calcifiers, ocean warming, and acidification are a growing threat to these organisms-impacting their morphology and function. Museum collections are useful in assessing long-term environmental impacts on organisms in a natural multi-stressor environment, where acclimation and adaptation can be considered. Using the American Museum of Natural History collections ranging from the early 1900s until now, we show that shell porosity changes through time. Shells collected today are significantly more porous than shells collected in the 1960s and, at some sites, than shells collected from the early 1900s. The disparity between porosity changes matches well with the warming that occurred over the last 130 years in the north Atlantic suggesting that warming is causing porosity changes. However, more work is required to discern local environmental impacts and to fully identify porosity drivers. Since, porosity is known to affect structural integrity, porosity increasing through time could have negative consequences for mussel reef structural integrity and hence habitat formation and storm defenses.


Subject(s)
Mytilus edulis , Mytilus , Animals , Industrial Development , Museums , Hydrogen-Ion Concentration , Calcification, Physiologic
20.
Int J Mol Sci ; 25(8)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38673767

ABSTRACT

The MC3T3-E1 preosteoblastic cell line is widely utilised as a reliable in vitro system to assess bone formation. However, the experimental growth conditions for these cells hugely diverge, and, particularly, the osteogenic medium (OSM)'s composition varies in research studies. Therefore, we aimed to define the ideal culture conditions for MC3T3-E1 subclone 4 cells with regard to their mineralization capacity and explore if oxidative stress or the cellular metabolism processes are implicated. Cells were treated with nine different combinations of long-lasting ascorbate (Asc) and ß-glycerophosphate (ßGP), and osteogenesis/calcification was evaluated at three different time-points by qPCR, Western blotting, and bone nodule staining. Key molecules of the oxidative and metabolic pathways were also assessed. It was found that sufficient mineral deposition was achieved only in the 150 µg.mL-1/2 mM Asc/ßGP combination on day 21 in OSM, and this was supported by Runx2, Alpl, Bglap, and Col1a1 expression level increases. NOX2 and SOD2 as well as PGC1α and Tfam were also monitored as indicators of redox and metabolic processes, respectively, where no differences were observed. Elevation in OCN protein levels and ALP activity showed that mineralisation comes as a result of these differences. This work defines the most appropriate culture conditions for MC3T3-E1 cells and could be used by other research laboratories in this field.


Subject(s)
Energy Metabolism , Osteoblasts , Osteogenesis , Oxidative Stress , Animals , Mice , Osteogenesis/drug effects , Osteoblasts/metabolism , Osteoblasts/cytology , Cell Line , Glycerophosphates/metabolism , Glycerophosphates/pharmacology , Calcification, Physiologic , Cell Differentiation , Cell Culture Techniques/methods , Ascorbic Acid/pharmacology , Ascorbic Acid/metabolism , Culture Media/chemistry , Culture Media/pharmacology
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