Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress

Peng, Yan; Qu, Rongmei; Feng, Yanting; Huang, Xiaolan; Yang, Yuchao; Fan, Tao; Sun, Bing; Khan, Asmat Ullah; Wu, Shutong; Dai, Jingxing; Ouyang, Jun

doi:10.1186/s13287-021-02597-y

Cited by 19 publications

(27 citation statements)

References 59 publications

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“…Here, we showed the early pSMAD1,5,9 is regulated both by β3 integrin and by N-cadherin (Figure 6). Our results are consistent with the role of β3 integrin in early osteogenic differentiation (Yuh et al, 2020), which is associated with tensile loading (Peng et al, 2021).…”

Section: Interplay Between N-cadherin/β3 Integrin and Cadherin11/β1 I...supporting

confidence: 91%

Interplay between integrins and cadherins to control bone differentiation upon BMP-2 stimulation

Valat¹,

Fourel²,

Sales

et al. 2023

Front. Cell Dev. Biol.

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Introduction: Upon BMP-2 stimulation, the osteoblastic lineage commitment in C2C12 myoblasts is associated with a microenvironmental change that occurs over several days. How does BMP-2 operate a switch in adhesive machinery to adapt to the new microenvironment and to drive bone cell fate is not well understood. Here, we addressed this question for BMP-2 delivered either in solution or physically bound of a biomimetic film, to mimic its presentation to cells via the extracellular matrix (ECM).Methods: Biommetics films were prepared using a recently developed automated method that enable high content studies of cellular processes. Comparative gene expressions were done using RNA sequencing from the encyclopedia of the regulatory elements (ENCODE). Gene expressions of transcription factors, beta chain (1, 3, 5) integrins and cadherins (M, N, and Cad11) were studied using quantitative PCR. ECM proteins and adhesion receptor expressions were also quantified by Western blots and dot blots. Their spatial organization in and around cells was studied using immuno-stainings. The individual effect of each receptor on osteogenic transcription factors and alkaline phosphatase expression were studied using silencing RNA of each integrin and cadherin receptor. The organization of fibronectin was studied using immuno-staining and quantitative microscopic analysis.Results: Our findings highlight a switch of integrin and cadherin expression during muscle to bone transdifferentiation upon BMP-2 stimulation. This switch occurs no matter the presentation mode, for BMP-2 presented in solution or via the biomimetic film. While C2C12 muscle cells express M-cadherin and Laminin-specific integrins, the BMP-2-induced transdifferentiation into bone cells is associated with an increase in the expression of cadherin-11 and collagen-specific integrins. Biomimetic films presenting matrix-bound BMP-2 enable the revelation of specific roles of the adhesive receptors depending on the transcription factor.Discussion: While β3 integrin and cadherin-11 work in concert to control early pSMAD1,5,9 signaling, β1 integrin and Cadherin-11 control RunX2, ALP activity and fibronectin organization around the cells. In contrast, while β1 integrin is also important for osterix transcriptional activity, Cadherin-11 and β5 integrin act as negative osterix regulators. In addition, β5 integrin negatively regulates RunX2. Our results show that biomimetic films can be used to delinate the specific events associated with BMP-2-mediated muscle to bone transdifferentiation. Our study reveals how integrins and cadherins work together, while exerting distinct functions to drive osteogenic programming. Different sets of integrins and cadherins have complementary mechanical roles during the time window of this transdifferentiation.

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Section: Interplay Between N-cadherin/β3 Integrin and Cadherin11/β1 I...supporting

confidence: 91%

Interplay between integrins and cadherins to control bone differentiation upon BMP-2 stimulation

Valat¹,

Fourel²,

Sales

et al. 2023

Front. Cell Dev. Biol.

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“…On the other hand, overexpression of a human p-FAK-Y407E phosphomimetic (i.e., constitutively active) mutant in human Sertoli cells is also capable of blocking the PFOS-induced MT defragmentation (23), such that MTs stretched across the entire human Sertoli cell cytosol, analogous to control human Sertoli cells (23). Collectively, these findings are consistent with earlier studies in fibroblasts, and epithelial and endothelial cells in which FAK is involved in actin and MT polymerization (74)(75)(76)(77)(78). In brief, these two activated/phosphorylated forms of FAK (and mTORC1, see Figure 2) appear to serve as molecular switch to turn the apical ES and BTB/basal ES "on" or "off", depending on their expression status at the microdomain of these sites across the seminiferous epithelium (Figures 2, 3).…”

Section: Introductionsupporting

confidence: 87%

Signaling Proteins That Regulate Spermatogenesis Are the Emerging Target of Toxicant-Induced Male Reproductive Dysfunction

Gao

Wang

et al. 2021

Front. Endocrinol.

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There is emerging evidence that environmental toxicants, in particular endocrine disrupting chemicals (EDCs) such as cadmium and perfluorooctanesulfonate (PFOS), induce Sertoli cell and testis injury, thereby perturbing spermatogenesis in humans, rodents and also widelife. Recent studies have shown that cadmium (e.g., cadmium chloride, CdCl2) and PFOS exert their disruptive effects through putative signaling proteins and signaling cascade similar to other pharmaceuticals, such as the non-hormonal male contraceptive drug adjudin. More important, these signaling proteins were also shown to be involved in modulating testis function based on studies in rodents. Collectively, these findings suggest that toxicants are using similar mechanisms that used to support spermatogenesis under physiological conditions to perturb Sertoli and testis function. These observations are physiologically significant, since a manipulation on the expression of these signaling proteins can possibly be used to manage the toxicant-induced male reproductive dysfunction. In this review, we highlight some of these findings and critically evaluate the possibility of using this approach to manage toxicant-induced defects in spermatrogenesis based on recent studies in animal models.

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“…In general, porous structures with a large surface area increase activation of integrin, which plays a critical role in cell adhesion and various cellular activities by transmitting signals via the cell membrane. Mechanical signals transduced into cells can initiate and regulate signaling pathways for osteogenic differentiation of cells . Birch et al reported that porous scaffolds with pore dimensions of about 3–6 μm enhanced adhesion and activation (i.e., mineralized ECM deposition) of osteoblasts.…”

Section: Resultsmentioning

confidence: 99%

“…Mechanical signals transduced into cells can initiate and regulate signaling pathways for osteogenic differentiation of cells. 62 Birch et al 63 reported that porous scaffolds with pore dimensions of about 3−6 μm enhanced adhesion and activation (i.e., mineralized ECM deposition) of osteoblasts. We also revealed that porous structures like stacked leaves on the sheet provided a suitable milieu for bone regeneration.…”

Section: Analysis Of Hpdcs Adhesion Onto Lss Particlesmentioning

confidence: 99%

Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration

Kim

Park

Lee

et al. 2022

ACS Biomater. Sci. Eng.

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Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.

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Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress

Cited by 19 publications

References 59 publications

Interplay between integrins and cadherins to control bone differentiation upon BMP-2 stimulation

Interplay between integrins and cadherins to control bone differentiation upon BMP-2 stimulation

Signaling Proteins That Regulate Spermatogenesis Are the Emerging Target of Toxicant-Induced Male Reproductive Dysfunction

Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration

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