Micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and secretion to improve osseointegration

Abstract Background Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo. Results We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation. Conclusions These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.

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Phenol red mimics biological actions of estradiol: Enhancement of osteoblast proliferation in vitro and of type I collagen gene expression in bone and uterus of rats in vivo

Journal of Steroid Biochemistry ◽

10.1016/0022-4731(89)90239-2 ◽

1989 ◽

Vol 33 (5) ◽

pp. 907-914 ◽

Cited By ~ 31

Author(s):

Matthias Ernst ◽

Christoph Schmid ◽

E.Rudolf Froesch

Keyword(s):

Gene Expression ◽

Type I Collagen ◽

Type I ◽

Collagen Gene ◽

Phenol Red ◽

Osteoblast Proliferation ◽

Proliferation In Vitro ◽

Biological Actions

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Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury.

Journal of Clinical Investigation ◽

10.1172/jci117017 ◽

1994 ◽

Vol 93 (2) ◽

pp. 652-661 ◽

Cited By ~ 87

Author(s):

S Takeshita ◽

D Gal ◽

G Leclerc ◽

J G Pickering ◽

R Riessen ◽

...

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Smooth Muscle ◽

Gene Transfer ◽

Smooth Muscle Cell ◽

Vascular Injury ◽

Rabbit Model ◽

Proliferation In Vitro

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Biomimetic titanium implant coated with extracellular matrix enhances and accelerates osteogenesis

Nanomedicine ◽

10.2217/nnm-2020-0047 ◽

2020 ◽

Vol 15 (18) ◽

pp. 1779-1793

Author(s):

Yu Wu ◽

Haikuo Tang ◽

Lin Liu ◽

Qianting He ◽

Luodan Zhao ◽

...

Keyword(s):

Bone Marrow ◽

Extracellular Matrix ◽

Stromal Cells ◽

Titanium Surface ◽

Titanium Implant ◽

Titanium Implants ◽

In Vivo Studies ◽

Calcium Deposition

Aim: To evaluate the biological function of titanium implants coated with cell-derived mineralized extracellular matrix, which mimics a bony microenvironment. Materials & methods: A biomimetic titanium implant was fabricated primarily by modifying the titanium surface with TiO2 nanotubes or sand-blasted, acid-etched topography, then was coated with mineralized extracellular matrix constructed by culturing bone marrow mesenchymal stromal cells. The osteogenic ability of biomimetic titanium surface in vitro and in vivo were evaluated. Results: In vitro and in vivo studies revealed that the biomimetic titanium implant enhanced and accelerated osteogenesis of bone marrow stromal cells by increasing cell proliferation and calcium deposition. Conclusion: By combining surface topography modification with biological coating, the results provided a valuable method to produce biomimetic titanium implants with excellent osteogenic ability.

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Hyperlipidemia Impairs Osseointegration via the ROS/Wnt/β-Catenin Pathway

Journal of Dental Research ◽

10.1177/0022034520983245 ◽

2021 ◽

pp. 002203452098324

Author(s):

Y.N. Wang ◽

T.T. Jia ◽

Y. Feng ◽

S.Y. Liu ◽

W.J. Zhang ◽

...

Keyword(s):

Titanium Surface ◽

Titanium Implant ◽

Titanium Implants ◽

Oxygen Species ◽

High Fat ◽

Promising Therapeutic Target ◽

Novel Drugs ◽

Underlying Mechanisms

The influence of hyperlipidemia on titanium implant osseointegration and the underlying mechanisms is not well understood. This study investigates the changes in osseointegration and explores the potential mechanisms in hyperlipidemia conditions. In vivo, specialized titanium implants were implanted in the femurs of diet-induced or genetic hyperlipidemia mice. In vitro, primary murine osteoblasts were cultured on the titanium surface in high-fat medium. Results showed that hyperlipidemia led to poor osseointegration in both types of mice in vivo, and high-fat medium impaired the osteogenic differentiation of primary osteoblasts on the titanium surface in vitro. In addition, high-fat medium caused significant overproduction of reactive oxygen species (ROS) and inhibition of the Wnt/β-catenin pathway in osteoblasts. Both N-acetyl-L-cysteine (NAC, an ROS antagonist) and Wnt3a (an activator of the Wnt/β-catenin pathway) attenuated the poor osteogenic ability of osteoblasts. In addition, NAC reactivated the Wnt/β-catenin pathway in osteoblasts under high-fat stimulation. These results demonstrate that hyperlipidemia impairs osseointegration via the ROS/Wnt/β-catenin pathway and provide support for the ROS or Wnt/β-catenin pathway as a promising therapeutic target for the development of novel drugs or implant materials to improve the osseointegration of implants in hyperlipidemic patients.

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The effect of hydrofluoric acid treatment of TiO2 grit blasted titanium implants on adherent osteoblast gene expression in vitro and in vivo

Biomaterials ◽

10.1016/j.biomaterials.2007.08.032 ◽

2007 ◽

Vol 28 (36) ◽

pp. 5418-5425 ◽

Cited By ~ 152

Author(s):

Juanli Guo ◽

Ricardo J. Padilla ◽

Wallace Ambrose ◽

Ingeborg J. De Kok ◽

Lyndon F. Cooper

Keyword(s):

Gene Expression ◽

Hydrofluoric Acid ◽

Acid Treatment ◽

Titanium Implants

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Transcription Factor ATF2 Cooperates with v-Jun To Promote Growth Factor-Independent Proliferation In Vitro and Tumor Formation In Vivo

Molecular and Cellular Biology ◽

10.1128/mcb.18.12.7020 ◽

1998 ◽

Vol 18 (12) ◽

pp. 7020-7029 ◽

Cited By ~ 32

Author(s):

Stéphanie Huguier ◽

Joël Baguet ◽

Sandrine Perez ◽

Hans van Dam ◽

Marc Castellazzi

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Tumor Formation ◽

Dependent Model ◽

Proliferation In Vitro ◽

Bzip Family ◽

Low Serum

ABSTRACT ATF2 belongs to the bZIP family of transcription factors and controls gene expression via 8-bp ATF/CREB motifs either as a homodimer or as a heterodimer—for instance, with Jun—but has never been shown to be directly involved in oncogenesis. Experiments were designed to evaluate a possible role of ATF2 in oncogenesis in chick embryo fibroblasts (CEFs) in the presence or absence of v-Jun. We found that (i) forced expression of ATF2 cannot alone cause transformation, (ii) overexpression of ATF2 plus v-Jun specifically stimulates v-Jun-induced growth in medium with a reduced amount of serum, and (iii) the efficiency of low-serum growth correlates with the activity of a Jun-ATF2-dependent model promoter in stably transformed CEFs. Analysis of ATF2 and Jun dimerization mutants showed that the growth-stimulatory effect of ATF2 is likely to be mediated by v-Jun–ATF2 heterodimers since (i) v-Jun-m1, a mutant with enhanced affinity for ATF2, induces growth in low-serum medium much more efficiently than v-Jun, when expressed alone or in combination with ATF2; and (ii) ATF2/fos, a mutant that efficiently binds to v-Jun but is unable to form stable homodimers, shows enhanced oncogenic cooperation with v-Jun. In addition, we examined the role of ATF2 in tumor formation by subcutaneous injection of CEFs into chickens. In contrast to v-Jun, v-Jun-m1 gave rise to numerous fibrosarcomas while coexpression of ATF2 and v-Jun-m1 led to a dramatic development of fibrosarcomas visible within 1 week. Together these data demonstrate that overexpressed ATF2 potentiates the ability of v-Jun-transformed CEFs to grow in low-serum medium in vitro and contributes to the formation of tumors in vivo.

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Identification of genes early responsive to gamma-irradiation in isolated rat hepatocytes in vitro and rat liver in vivo by cDNA array gene expression analysis

Zeitschrift für Gastroenterologie ◽

10.1055/s-2005-920060 ◽

2005 ◽

Vol 43 (05) ◽

Author(s):

DS Batusic ◽

H Christiansen ◽

B Saile ◽

RM Hermann ◽

J Dudas ◽

...

Keyword(s):

Gene Expression ◽

Gamma Irradiation ◽

Rat Liver ◽

Gene Expression Analysis ◽

Cdna Array ◽

Rat Hepatocytes ◽

Isolated Rat Hepatocytes ◽

Isolated Rat

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Effect of X-irradiation on gene expression of rat liver chemokines: in vivo and in vitro studies

Zeitschrift für Gastroenterologie ◽

10.1055/s-2008-1037499 ◽

2008 ◽

Vol 46 (01) ◽

Cited By ~ 1

Author(s):

F Moriconi ◽

H Christiansen ◽

N Sheikh ◽

J Dudas ◽

...

Keyword(s):

Gene Expression ◽

Rat Liver ◽

In Vitro Studies ◽

X Irradiation

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Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon

Diseases of Aquatic Organisms ◽

10.3354/dao03475 ◽

2020 ◽

Vol 139 ◽

pp. 153-160

Author(s):

S Peeralil ◽

TC Joseph ◽

V Murugadas ◽

PG Akhilnath ◽

VN Sreejith ◽

...

Keyword(s):

Gene Expression ◽

Virulence Genes ◽

Vibrio Harveyi ◽

Penaeus Monodon ◽

Challenge Test ◽

Virulence Gene ◽

Economic Losses ◽

Virulence Gene Expression

Luminescent Vibrio harveyi is common in sea and estuarine waters. It produces several virulence factors and negatively affects larval penaeid shrimp in hatcheries, resulting in severe economic losses to shrimp aquaculture. Although V. harveyi is an important pathogen of shrimp, its pathogenicity mechanisms have yet to be completely elucidated. In the present study, isolates of V. harveyi were isolated and characterized from diseased Penaeus monodon postlarvae from hatcheries in Kerala, India, from September to December 2016. All 23 tested isolates were positive for lipase, phospholipase, caseinase, gelatinase and chitinase activity, and 3 of the isolates (MFB32, MFB71 and MFB68) showed potential for significant biofilm formation. Based on the presence of virulence genes, the isolates of V. harveyi were grouped into 6 genotypes, predominated by vhpA+ flaB+ ser+ vhh1- luxR+ vopD- vcrD+ vscN-. One isolate from each genotype was randomly selected for in vivo virulence experiments, and the LD50 ranged from 1.7 ± 0.5 × 103 to 4.1 ± 0.1 × 105 CFU ml-1. The expression of genes during the infection in postlarvae was high in 2 of the isolates (MFB12 and MFB32), consistent with the result of the challenge test. However, in MFB19, even though all genes tested were present, their expression level was very low and likely contributed to its lack of virulence. Because of the significant variation in gene expression, the presence of virulence genes alone cannot be used as a marker for pathogenicity of V. harveyi.

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