Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography

Lopes, Helena Bacha; Freitas, Gileade Pereira; Elias, Carlos Nelson; Tye, Coralee E.; Stein, Janet L.; Lian, Jane B.; Rosa, Adalberto Luiz; Beloti, Márcio Mateus

doi:10.1002/jbm.a.36643

Cited by 30 publications

(29 citation statements)

References 43 publications

(106 reference statements)

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“…GSEA revealed that the integrin pathway and cytoskeletal organisation were enriched in MSCs. One study reported that integrin enhanced the differentiation of MSCs into osteoblast [ 53 ]. Other studies also confirmed the roles of integrin pathway in MSC differentiation [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF

et al. 2020

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Introduction Mesenchymal stem cells (MSCs) isolated from bone marrow have different developmental origins, including neural crest. MSCs can differentiate into neural progenitor-like cells (NPCs) under the influence of bFGF and EGF. NPCs can terminally differentiate into neurons that express beta-III-tubulin and elicit action potential. The main aim of the study was to identify key genetic markers involved in differentiation of MSCs into NPCs through transcriptomic analysis. Method Total RNA was isolated from MSCs and MSCs-derived NPCs followed by cDNA library construction for transcriptomic analysis. Sample libraries that passed the quality and quantity assessments were subjected to high throughput mRNA sequencing using NextSeq®500. Differential gene expression analysis was performed using the DESeq2 R package with MSC samples being a reference group. The expression of eight differentially regulated genes was counter validated using real-time PCR. Results In total, of the 3,252 differentially regulated genes between MSCs and NPCs with two or more folds, 1,771 were upregulated genes, whereas 1,481 were downregulated in NPCs. Amongst these differential genes, 104 transcription factors were upregulated, and 45 were downregulated in NPCs. Neurogenesis related genes were upregulated in NPCs and the main non-redundant gene ontology (GO) terms enriched in NPCs were the autonomic nervous system, cell surface receptor signalling pathways), extracellular structure organisation, and programmed cell death. The main non-redundant GO terms enriched in MSCs included cytoskeleton organisation cytoskeleton structural constituent, mitotic cell cycle), and the mitotic cell cycle process Gene set enrichment analysis also confirmed cell cycle regulated pathways as well as Biocarta integrin pathway were upregulated in MSCs. Transcription factors enrichment analysis by ChEA3 revealed Foxs1 and HEYL, amongst the top five transcription factors, inhibits and enhances, respectively, the NPCs differentiation of MSCs. Conclusions The vast differences in the transcriptomic profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.

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Section: Discussionmentioning

confidence: 99%

Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF

et al. 2020

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“…Several studies have demonstrated the participation of the integrin signaling pathway, through FAK, in response of osteoblastic cells to different surface topographies. [9][10][11][12][13][14][15][16] Thus, the role of specific FAK inhibitors in the osteogenic potential of cells on Ti surfaces is an interesting research topic. The present study aimed to investigate the participation of FAK in interactions between osteoblastic cells and Ti surfaces with different topographies by using a specific FAK inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Effect of focal adhesion kinase inhibition on osteoblastic cells grown on titanium with different topographies

et al. 2020

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Objective: The present study aimed to investigate the participation of focal adhesion kinases (FAK) in interactions between osteoblastic cells and titanium (Ti) surfaces with three different topographies, namely, untreated (US), microstructured (MS), and nanostructured (NS). Methodology: Osteoblasts harvested from the calvarial bones of 3-day-old rats were cultured on US, MS and NS discs in the presence of PF-573228 (FAK inhibitor) to evaluate osteoblastic differentiation. After 24 h, we evaluated osteoblast morphology and vinculin expression, and on day 10, the following parameters: gene expression of osteoblastic markers and integrin signaling components, FAK protein expression and alkaline phosphatase (ALP) activity. A smooth surface, porosities at the microscale level, and nanocavities were observed in US, MS, and NS, respectively. Results: FAK inhibition decreased the number of filopodia in cells grown on US and MS compared with that in NS. FAK inhibition decreased the gene expression of Alp, bone sialoprotein, osteocalcin, and ALP activity in cells grown on all evaluated surfaces. FAK inhibition did not affect the gene expression of Fak, integrin alpha 1 (Itga1) and integrin beta 1 (Itgb1) in cells grown on MS, increased the gene expression of Fak in cells grown on NS, and increased the gene expression of Itga1 and Itgb1 in cells grown on US and NS. Moreover, FAK protein expression decreased in cells cultured on US but increased in cells cultured on MS and NS after FAK inhibition; no difference in the expression of vinculin was observed among cells grown on all surfaces. Conclusions: Our data demonstrate the relevance of FAK in the interactions between osteoblastic cells and Ti surfaces regardless of surface topography. Nanotopography positively regulated FAK expression and integrin signaling pathway components during osteoblast differentiation.In this context, the development of Ti surfaces with the ability to upregulate FAK activity could positively impact the process of implant osseointegration.

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“…Martinez et al (2018) showed that, when osteoblasts were grown into a nanotopography, greater cell spreading, proliferation, and viability, as well as increased expression of two proteins involved in the initial osseointegration process were observed, when compared with a surface treated by double etching alone. Furthermore, other studies depicted the benefits of NANO surface (de Oliveira, Zalzal, Beloti, Rosa, & Nanci, 2007; Jimbo et al, 2011; Longo et al, 2016; Lopes et al, 2019b; Lopes et al, 2020). In the present study, gene expression (Runx2, Alp and Opn) and micro‐CT (BV/TV, BIC, BS/BV and Po.To) analysis revealed the superiority of NANO surface when compared to machined and DAE (data as a function of implant surface).…”

Section: Discussionmentioning

confidence: 95%

Influence of nano‐hydroxyapatite coating implants on gene expression of osteogenic markers andmicro‐CTparameters. An in vivo study in diabetic rats

Oliveira

Soares

Souza

et al. 2020

J Biomedical Materials Res

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This study evaluated the response of a nano‐hydroxyapatite coating implant through gene expression analysis (runt‐related transcription factor 2 (Runx2), alkaline phosphatase (Alp), osteopontin (Opn), osteocalcin (Oc), receptor activator of nuclear factor‐kappa B (Rank), receptor activator of nuclear factor‐kappa B ligand (Rank‐L), and osteoprotegerin (Opg)). Three‐dimensional evaluation (percent bone volume (BV/TV); percent intersection surface (BIC); bone surface/volume ratio (BS/BV); and total porosity (To.Po)) were also analyzed. Mini implants were surgically placed in tibias of both healthy and diabetic rats. The animals were euthanized at 7 and 30 days. Evaluating all factors the relative expression of Rank showed that NANO surface presented the best results at 7 days (diabetic rats). Furthermore the levels of Runx2, Alp, Oc, and Opn suggest an increase in osteoblasts proliferation, especially in early stages of osseointegration. %BIC in healthy and diabetic (7 days) depicted statistically significant differences for NANO group. BV/TV, BS/BV and To.Po demonstrated higher values for NANO group in all evaluated time point and irrespective of systemic condition, but BS/BV 30 days (healthy rat) and 7 and 30 days (diabetic rat). Microtomographic and gene expression analyses have shown the benefits of nano‐hydroxyapatite coated implants in promoting new bone formation in diabetic rats.

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Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography

Cited by 30 publications

References 43 publications

Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF

Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF

Effect of focal adhesion kinase inhibition on osteoblastic cells grown on titanium with different topographies

Influence of nano‐hydroxyapatite coating implants on gene expression of osteogenic markers andmicro‐CTparameters. An in vivo study in diabetic rats

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