Osteoblasts grown on microroughened titanium surfaces regulate angiogenic growth factor production through specific integrin receptors

Raines, Andrew L.; Berger, Michael B.; Schwartz, Zvi; Boyan, Barbara D.

doi:10.1016/j.actbio.2019.07.036

Cited by 29 publications

(31 citation statements)

References 44 publications

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“…Therefore, integrin α2 mediated osteogenic differentiation could be considered topography specific, and in the existing three surfaces, only hierarchical micro-nano topography (SLM-AHT) could activate this process. And our finding helps to endorse the recently proposed possible function of integrin α2 in bone formation (Leem et al, 2016;Raines et al, 2019).…”

Section: Discussionsupporting

confidence: 85%

“…Among them, integrin α2 is considered playing an important role in regulating cell adhesion and osteogenic differentiation (Olivares-Navarrete et al, 2015). Knockdown of α2 integrin subunits inhibited the formation of osteogenic microenvironment (Raines et al, 2019). And it was also reported that integrin α2 is required for activation of Runx2, the following expression of Ocn, and ECM mineralization procedure (Siebers et al, 2005;Hui-Min, Hu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

Zheng

Tian

Gao

et al. 2020

Front. Bioeng. Biotechnol.

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Surface topography dictates important aspects of cell biological behaviors. In our study, hierarchical micro-nano topography (SLM-AHT) with micro-scale grooves and nano-scale pores was fabricated and compared with smooth topography (S) and irregular micro-scale topography (SLA) surfaces to investigate mechanism involved in cell-surface interactions. Integrin α2 had a higher expression level on SLM-AHT surface compared with S and SLA surfaces, and the expression levels of osteogenic markers icluding Runx2, Col1a1, and Ocn were concomitantly upregulated on SLM-AHT surface. Moreover, formation of mature focal adhesions were significantly enhanced in SLM-AHT group. Noticablely, silencing integrin α2 could wipe out the difference of osteogenic gene expression among surfaces with different topography, indicating a crucial role of integrin α2 in topography induced osteogenic differentiation. In addition, PI3K-AKT signaling was proved to be regulated by integrin α2 and consequently participate in this process. Taken together, our findings illustrated that integrin α2-PI3K-AKT signaling axis plays a key role in hierarchical micro-nano topography promoting cell adhesion and osteogenic differentiation.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

Zheng

Tian

Gao

et al. 2020

Front. Bioeng. Biotechnol.

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“…There is no bone formation without a prior formation of newly -formed blood vessels. The existence of blood vessels shows a vital role in bone renewal processes and in implant osseointegration (Beltran-Partida et al, 2017;Genova et al, 2019;Raines et al, 2019b). The relationship between the complex molecular mechanisms of blood vessels and bone formation is still relatively unexplored, and a better understanding of these features would be welcomed.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between the complex molecular mechanisms of blood vessels and bone formation is still relatively unexplored, and a better understanding of these features would be welcomed. Recent studies have reported a close relationship between MSCs and endothelial cell, improving vasculogenesis (Genova et al, 2019;Raines et al, 2019b). It has been hypothesized that changes in the microstructure of implant surface could have a relationship with the secretion by osteoprogenitor cells of pro-angiogenic substances (Raines et al, 2019a).…”

Section: Introductionmentioning

confidence: 99%

Enhanced VEGF/VEGF-R and RUNX2 Expression in Human Periodontal Ligament Stem Cells Cultured on Sandblasted/Etched Titanium Disk

Marconi

Diomede

Pizzicannella³

et al. 2020

Front. Cell Dev. Biol.

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Bone formation, in skeletal development or in osseointegration processes, is the result of interaction between angiogenesis and osteogenesis. To establish osseointegration, cells must attach to the implant in a direct way without any deposition of soft tissue. Structural design and surface topography of dental implants enhance the cell attachment and can affect the biological response. The aim of the study was to evaluate the cytocompatibility, osteogenic and angiogenic markers involved in bone differentiation of human periodontal ligament stem cells (hPDLSCs) on different titanium disks surfaces. The hPDLSCs were cultured on pure titanium surfaces modified with two different procedures, sandblasted (Control-CTRL) and sandblasted/etched (Test-TEST) as experimental titanium surfaces. After 1 and 8 weeks of culture VEGF, VEGF-R, and RUNX2 expression was evaluated under confocal laser scanning microscopy. To confirm the obtained data, RT-PCR and WB analyses were performed in order to evaluate the best implant surface performance. TEST surfaces compared to CTRL titanium surfaces enhanced cell adhesion and increased VEGF and RUNX2 expression. Moreover, titanium TEST surfaces showed a different topographic morphology that promoted cell adhesion, proliferation, and osteogenic/angiogenic commitment. To conclude, TEST surfaces performed more efficiently than CTRL surfaces; furthermore, TEST surface results showed them to be more biocompatible, better tolerated, and appropriate for allowing hPDLSC growth and proliferation. This fact could also lead to more rapid bone-titanium integration.

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“…Ordinary titanium surfaces are electronegative in nature, as are cells [ 7 ]. Therefore, titanium surfaces attract cells only in the presence of divalent cations, such as Ca 2+ [ 26 , 27 ]. However, UV-treated titanium surfaces are positively charged and act as chemoattractants that aggressively attract cells necessary for bone-implant integration, without the aid of divalent cations [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

UV-Pre-Treated and Protein-Adsorbed Titanium Implants Exhibit Enhanced Osteoconductivity

Sugita

Saruta

Taniyama

et al. 2020

IJMS

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Titanium materials are essential treatment modalities in the medical field and serve as a tissue engineering scaffold and coating material for medical devices. Thus, there is a significant demand to improve the bioactivity of titanium for therapeutic and experimental purposes. We showed that ultraviolet light (UV)-pre-treatment changed the protein-adsorption ability and subsequent osteoconductivity of titanium. Fibronectin (FN) adsorption on UV-treated titanium was 20% and 30% greater after 1-min and 1-h incubation, respectively, than that of control titanium. After 3-h incubation, FN adsorption on UV-treated titanium remained 30% higher than that on the control. Osteoblasts were cultured on titanium disks after 1-h FN adsorption with or without UV-pre-treatment and on titanium disks without FN adsorption. The number of attached osteoblasts during the early stage of culture was 80% greater on UV-treated and FN-adsorbed (UV/FN) titanium than on FN-adsorbed (FN) titanium; osteoblasts attachment on UV/FN titanium was 2.6- and 2.1-fold greater than that on control- and UV-treated titanium, respectively. The alkaline phosphatase activity of osteoblasts on UV/FN titanium was increased 1.8-, 1.8-, and 2.4-fold compared with that on FN-adsorbed, UV-treated, and control titanium, respectively. The UV/FN implants exhibited 25% and 150% greater in vivo biomechanical strength of bone integration than the FN- and control implants, respectively. Bone morphogenetic protein-2 (BMP-2) adsorption on UV-treated titanium was 4.5-fold greater than that on control titanium after 1-min incubation, resulting in a 4-fold increase in osteoblast attachment. Thus, UV-pre-treatment of titanium accelerated its protein adsorptivity and osteoconductivity, providing a novel strategy for enhancing its bioactivity.

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Osteoblasts grown on microroughened titanium surfaces regulate angiogenic growth factor production through specific integrin receptors

Cited by 29 publications

References 44 publications

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

Enhanced VEGF/VEGF-R and RUNX2 Expression in Human Periodontal Ligament Stem Cells Cultured on Sandblasted/Etched Titanium Disk

UV-Pre-Treated and Protein-Adsorbed Titanium Implants Exhibit Enhanced Osteoconductivity

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