Human foetal osteoblastic cell response to polymer-demixed nanotopographic interfaces

Nanoscale cell–substratum interactions are of significant interest in various biomedical applications. We investigated human foetal osteoblastic cell response to randomly distributed nanoisland topography with varying heights (11, 38 and 85 nm) produced by a polystyrene (PS)/polybromostyrene polymer-demixing technique. Cells displayed island-conforming lamellipodia spreading, and filopodia projections appeared to play a role in sensing the nanotopography. Cells cultured on 11 nm high islands displayed significantly enhanced cell spreading and larger cell dimensions than cells on larger nanoislands or flat PS control, on which cells often displayed a stellate shape. Development of signal transmitting structures such as focal adhesive vinculin protein and cytoskeletal actin stress fibres was more pronounced, as was their colocalization, in cells cultured on smaller nanoisland surfaces. Cell adhesion and proliferation were greater with decreasing island height. Alkaline phosphatase (AP) activity, an early stage marker of bone cell differentiation, also exhibited nanotopography dependence, i.e. higher AP activity on 11 nm islands compared with that on larger islands or flat PS. Therefore, randomly distributed island topography with varying nanoscale heights not only affect adhesion-related cell behaviour but also bone cell phenotype. Our results suggest that modulation of nanoscale topography may be exploited to control cell function at cell–biomaterial interfaces.

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Concepts of Osteoblast Growth and Differentiation: Basis for Modulation of Bone Cell Development and Tissue Formation

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411920030030501 ◽

1992 ◽

Vol 3 (3) ◽

pp. 269-305 ◽

Cited By ~ 410

Author(s):

Jane B. Lian ◽

Gary S. Stein

Keyword(s):

Gene Expression ◽

Cell Growth ◽

Three Dimensional ◽

Bone Cell ◽

Cell Phenotype ◽

Specific Gene ◽

Gene Promoters ◽

Developmental Sequence ◽

Combined Application ◽

Bone Cell Differentiation

The combined application of molecular, biochemical, histochemical, and ultrastructural approaches has defined a temporal sequence of gene expression associated with development of the bone cell phenotype in primary osteoblast cultures. The peak levels of expressed genes reflect a developmental sequence of bone cell differentiation characterized by three principal periods: proliferation, extracellular matrix maturation and mineralization, and two restriction points to which the cells can progress but cannot pass without further signals. The regulation of cell growth and bone-specific gene expression has been examined during this developmental sequence and is discussed within the context of several unique concepts. These are (1) that oncogene expression in proliferating osteoblasts contributes to the suppression of genes expressed postproliferatively, (2) that hormone modulation of a gene is dependent upon the maturational state of the osteoblast, and (3) that chromatin structure and the presence of nucleosomes contribute to three-dimensional organization of gene promoters that support synergistic and/or antagonistic activities of physiologic mediators of bone cell growth and differentiation.

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Relevance of the sterilization-induced effects on the properties of different hydroxyapatite nanoparticles and assessment of the osteoblastic cell response

Journal of The Royal Society Interface ◽

10.1098/rsif.2012.0487 ◽

2012 ◽

Vol 9 (77) ◽

pp. 3397-3410 ◽

Cited By ~ 26

Author(s):

C. Santos ◽

P. S. Gomes ◽

J. A. Duarte ◽

R. P. Franke ◽

M. M. Almeida ◽

...

Keyword(s):

Bone Tissue ◽

Cell Response ◽

Bone Cell ◽

Osteoblastic Cells ◽

Osteoblastic Cell ◽

Aggregation State ◽

Cytoskeleton Organization ◽

Wet Chemical Synthesis ◽

Nanoparticle Aggregates

Hydroxyapatite (Hap) is a calcium phosphate with a chemical formula that closely resembles that of the mineral constituents found in hard tissues, thereby explaining its natural biocompatibility and wide biomedical use. Nanostructured Hap materials appear to present a good performance in bone tissue applications because of their ability to mimic the dimensions of bone components. However, bone cell response to individual nanoparticles and/or nanoparticle aggregates lost from these materials is largely unknown and shows great variability. This work addresses the preparation and characterization of two different Hap nanoparticles and their interaction with osteoblastic cells. Hap particles were produced by a wet chemical synthesis (WCS) at 37°C and by hydrothermal synthesis (HS) at 180°C. As the ultimate in vivo applications require a sterilization step, the synthesized particles were characterized ‘as prepared’ and after sterilization (autoclaving, 120°C, 20 min). WCS and HS particles differ in their morphological (size and shape) and physicochemical properties. The sterilization modified markedly the shape, size and aggregation state of WCS nanoparticles. Both particles were readily internalized by osteoblastic cells by endocytosis, and showed a low intracellular dissolution rate. Concentrations of WCS and HS particles less than 500 μg ml −1 did not affect cell proliferation, F-actin cytoskeleton organization and apoptosis rate and increased the gene expression of alkaline phosphatase and BMP-2. The two particles presented some differences in the elicited cell response. In conclusion, WCS and HS particles might exhibit an interesting profile for bone tissue applications. Results suggest the relevance of a proper particle characterization, and the interest of an individual nanoparticle targeted research.

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Analysis of trabecular bone structure demonstrates new mechanisms of bone cell function in primary hyperparathyroidism

Acta Endocrinologica ◽

10.1530/acta.0.117s083 ◽

1988 ◽

Vol 117 (4_Suppl) ◽

pp. S83 ◽

Cited By ~ 1

Author(s):

M. VOGEL ◽

M. HAHN ◽

G. DELLING

Keyword(s):

Primary Hyperparathyroidism ◽

Trabecular Bone ◽

Cell Function ◽

Bone Structure ◽

Bone Cell ◽

Trabecular Bone Structure

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Characterisation of the T-cell response to Ebola virus glycoprotein amongst survivors of the 2013–16 West Africa epidemic

Nature Communications ◽

10.1038/s41467-021-21411-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

T. R. W. Tipton ◽

Y. Hall ◽

J. A. Bore ◽

A. White ◽

L. S. Sibley ◽

...

Keyword(s):

T Cell ◽

West Africa ◽

Cell Response ◽

Ebola Virus ◽

Medical Condition ◽

Virus Disease ◽

T Cell Response ◽

Ebola Virus Disease ◽

Cell Phenotype ◽

T Cell Epitopes

AbstractZaireebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013–16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4+ or CD8+ T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.

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Nanostructure of bioactive glass affects bone cell attachment via protein restructuring upon adsorption

Scientific Reports ◽

10.1038/s41598-021-85050-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ukrit Thamma ◽

Tia J. Kowal ◽

Matthias M. Falk ◽

Himanshu Jain

Keyword(s):

Bioactive Glass ◽

Cell Response ◽

Interfacial Layer ◽

Cell Attachment ◽

Bone Cell ◽

Nano Structure ◽

Rgd Sequence ◽

Engineered Tissue ◽

Α Helix ◽

Β Sheet

AbstractThe nanostructure of engineered bioscaffolds has a profound impact on cell response, yet its understanding remains incomplete as cells interact with a highly complex interfacial layer rather than the material itself. For bioactive glass scaffolds, this layer comprises of silica gel, hydroxyapatite (HA)/carbonated hydroxyapatite (CHA), and absorbed proteins—all in varying micro/nano structure, composition, and concentration. Here, we examined the response of MC3T3-E1 pre-osteoblast cells to 30 mol% CaO–70 mol% SiO2 porous bioactive glass monoliths that differed only in nanopore size (6–44 nm) yet resulted in the formation of HA/CHA layers with significantly different microstructures. We report that cell response, as quantified by cell attachment and morphology, does not correlate with nanopore size, nor HA/CHO layer micro/nano morphology, or absorbed protein amount (bovine serum albumin, BSA), but with BSA’s secondary conformation as indicated by its β-sheet/α-helix ratio. Our results suggest that the β-sheet structure in BSA interacts electrostatically with the HA/CHA interfacial layer and activates the RGD sequence of absorbed adhesion proteins, such as fibronectin and vitronectin, thus significantly enhancing the attachment of cells. These findings provide new insight into the interaction of cells with the scaffolds’ interfacial layer, which is vital for the continued development of engineered tissue scaffolds.

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Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

International Journal of Molecular Sciences ◽

10.3390/ijms22157917 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7917

Author(s):

Hideaki Kaneto ◽

Tomohiko Kimura ◽

Masashi Shimoda ◽

Atsushi Obata ◽

Junpei Sanada ◽

...

Keyword(s):

Large Scale ◽

Cell Function ◽

Apoptotic Cell ◽

Early Stage ◽

Insulin Biosynthesis ◽

Protective Effects ◽

Pancreatic Β Cell ◽

Β Cells ◽

Β Cell ◽

Glucose Toxicity

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

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Cadmium toxicity: A role in bone cell function and teeth development

The Science of The Total Environment ◽

10.1016/j.scitotenv.2020.144646 ◽

2021 ◽

Vol 769 ◽

pp. 144646

Author(s):

Yonggang Ma ◽

Di Ran ◽

Xueni Shi ◽

Hongyan Zhao ◽

Zongping Liu

Keyword(s):

Cell Function ◽

Cadmium Toxicity ◽

Bone Cell ◽

Teeth Development

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Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

Bioengineering ◽

10.3390/bioengineering8010004 ◽

2020 ◽

Vol 8 (1) ◽

pp. 4

Author(s):

Devan L. Puhl ◽

Jessica L. Funnell ◽

Derek W. Nelson ◽

Manoj K. Gottipati ◽

Ryan J. Gilbert

Keyword(s):

Nervous System ◽

Glial Cell ◽

Cell Response ◽

Electrospun Fiber ◽

Neural Regeneration ◽

Cell Phenotype ◽

Comprehensive Overview ◽

Fiber Alignment ◽

Wide Range ◽

Fiber Scaffolds

Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide contact guidance for regenerating axons. Glia are non-neuronal regulatory cells that maintain homeostasis in the healthy nervous system and regulate regeneration in the injured nervous system. Electrospun fiber scaffolds offer a wide range of characteristics, such as fiber alignment, diameter, surface nanotopography, and surface chemistry that can be engineered to achieve a desired glial cell response to injury. Further, electrospun fibers can be loaded with drugs, nucleic acids, or proteins to provide the local, sustained release of such therapeutics to alter glial cell phenotype to better support regeneration. This review provides the first comprehensive overview of how electrospun fiber alignment, diameter, surface nanotopography, surface functionalization, and therapeutic delivery affect Schwann cells in the peripheral nervous system and astrocytes, oligodendrocytes, and microglia in the central nervous system both in vitro and in vivo. The information presented can be used to design and optimize electrospun fiber scaffolds to target glial cell response to mitigate nervous system injury and improve regeneration.

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