Modulation of BMP signalling by integrins

2016 ◽  
Vol 44 (5) ◽  
pp. 1465-1473 ◽  
Author(s):  
Hilary L. Ashe

The bone morphogenetic protein (BMP) pathway is a major conserved signalling pathway with diverse roles in development and homeostasis. Given that cells exist in three-dimensional environments, one important area is to understand how the BMP pathway operates within such complex cellular environments. The extracellular matrix contains information regarding tissue architecture and its mechanical properties that is transmitted to the cell via integrin receptors. In this review, I describe various examples of modulation of the BMP pathway by integrins. In the case of the Drosophila embryo and some cell line-based studies, integrins have been found to enhance BMP responses through different mechanisms, such as enhancement of BMP ligand–receptor binding and effects on Smad phosphorylation or stability. In these contexts, BMP-dependent activation of integrins is a common theme. However, I also discuss examples where integrins inhibit the BMP pathway, highlighting the context-dependent nature of integrin–BMP cross-talk.

Open Biology ◽  
2014 ◽  
Vol 4 (5) ◽  
pp. 140065 ◽  
Author(s):  
Lina Herhaus ◽  
Mazin A. Al-Salihi ◽  
Kevin S. Dingwell ◽  
Timothy D. Cummins ◽  
Lize Wasmus ◽  
...  

Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi -mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and transcription during Xenopus embryogenesis.


2021 ◽  
Author(s):  
Martijn AJ Koppens ◽  
Hayley Davis ◽  
Gabriel N Valbuena ◽  
Eoghan J Mulholland ◽  
Nadia Nasreddin ◽  
...  

ABSTRACTIn the intestine, the homeostatic effect of Bone Morphogenetic Protein (BMP) on cell fate has predominantly been inferred through pathway inactivation. Here, we assessed the impact of autocrine Bmp4 expression on secretory cell fate. Ligand exposure reduced proliferation, expedited terminal differentiation, abrogated long-term secretory cell survival and prevented dedifferentiation. As stem cell plasticity is required for regenerative adaptive reprogramming, we spatiotemporally mapped and functionally explored BMP’s role in epithelial restitution. Following ulceration, physiological attenuation of BMP signalling arose through upregulation of the secreted antagonist, Grem1, from topographically distinct populations of stromal cells. Concomitant expression supported functional compensation, following Grem1 deletion from tissue-resident fibroblasts. BMP pathway manipulation showed that antagonist-mediated BMP attenuation was obligatory, but functionally sub-maximal, as regeneration was impaired or enhanced by epithelial overexpression of Bmp4 or Grem1 respectively. Mechanistically, Bmp4 abrogated regenerative stem cell reprogramming, despite a convergent impact of YAP/TAZ on cell fate in remodelled wounds.


2019 ◽  
Vol 14 (8) ◽  
pp. 828-830 ◽  
Author(s):  
Weihua Meng ◽  
Weihong Wu ◽  
Weiwei Zhang ◽  
Luyao Cheng ◽  
Yunhong Jiao ◽  
...  

2021 ◽  
Vol 22 (7) ◽  
pp. 3391
Author(s):  
Sylwia Grabska-Zielińska ◽  
Alina Sionkowska ◽  
Ewa Olewnik-Kruszkowska ◽  
Katarzyna Reczyńska ◽  
Elżbieta Pamuła

The aim of this work was to compare physicochemical properties of three dimensional scaffolds based on silk fibroin, collagen and chitosan blends, cross-linked with dialdehyde starch (DAS) and dialdehyde chitosan (DAC). DAS was commercially available, while DAC was obtained by one-step synthesis. Structure and physicochemical properties of the materials were characterized using Fourier transfer infrared spectroscopy with attenuated total reflectance device (FTIR-ATR), swelling behavior and water content measurements, porosity and density observations, scanning electron microscopy imaging (SEM), mechanical properties evaluation and thermogravimetric analysis. Metabolic activity with AlamarBlue assay and live/dead fluorescence staining were performed to evaluate the cytocompatibility of the obtained materials with MG-63 osteoblast-like cells. The results showed that the properties of the scaffolds based on silk fibroin, collagen and chitosan can be modified by chemical cross-linking with DAS and DAC. It was found that DAS and DAC have different influence on the properties of biopolymeric scaffolds. Materials cross-linked with DAS were characterized by higher swelling ability (~4000% for DAS cross-linked materials; ~2500% for DAC cross-linked materials), they had lower density (Coll/CTS/30SF scaffold cross-linked with DAS: 21.8 ± 2.4 g/cm3; cross-linked with DAC: 14.6 ± 0.7 g/cm3) and lower mechanical properties (maximum deformation for DAC cross-linked scaffolds was about 69%; for DAS cross-linked scaffolds it was in the range of 12.67 ± 1.51% and 19.83 ± 1.30%) in comparison to materials cross-linked with DAC. Additionally, scaffolds cross-linked with DAS exhibited higher biocompatibility than those cross-linked with DAC. However, the obtained results showed that both types of scaffolds can provide the support required in regenerative medicine and tissue engineering. The scaffolds presented in the present work can be potentially used in bone tissue engineering to facilitate healing of small bone defects.


Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2239
Author(s):  
Nicholas Rodriguez ◽  
Samantha Ruelas ◽  
Jean-Baptiste Forien ◽  
Nikola Dudukovic ◽  
Josh DeOtte ◽  
...  

Recent advances in additive manufacturing, specifically direct ink writing (DIW) and ink-jetting, have enabled the production of elastomeric silicone parts with deterministic control over the structure, shape, and mechanical properties. These new technologies offer rapid prototyping advantages and find applications in various fields, including biomedical devices, prosthetics, metamaterials, and soft robotics. Stereolithography (SLA) is a complementary approach with the ability to print with finer features and potentially higher throughput. However, all high-performance silicone elastomers are composites of polysiloxane networks reinforced with particulate filler, and consequently, silicone resins tend to have high viscosities (gel- or paste-like), which complicates or completely inhibits the layer-by-layer recoating process central to most SLA technologies. Herein, the design and build of a digital light projection SLA printer suitable for handling high-viscosity resins is demonstrated. Further, a series of UV-curable silicone resins with thiol-ene crosslinking and reinforced by a combination of fumed silica and MQ resins are also described. The resulting silicone elastomers are shown to have tunable mechanical properties, with 100–350% elongation and ultimate tensile strength from 1 to 2.5 MPa. Three-dimensional printed features of 0.4 mm were achieved, and complexity is demonstrated by octet-truss lattices that display negative stiffness.


Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1217
Author(s):  
Jang Ho Ha ◽  
Jae Hyun Lim ◽  
Ji Woon Kim ◽  
Hyeon-Yeol Cho ◽  
Seok Geun Jo ◽  
...  

Blended hydrogels play an important role in enhancing the properties (e.g., mechanical properties and conductivity) of hydrogels. In this study, we generated a conductive blended hydrogel, which was achieved by mixing gelatin methacrylate (GelMA) with collagen, and silver nanowire (AgNW). The ratio of GelMA, collagen and AgNW was optimized and was subsequently gelated by ultraviolet light (UV) and heat. The scanning electron microscope (SEM) image of the conductive blended hydrogels showed that collagen and AgNW were present in the GelMA hydrogel. Additionally, rheological analysis indicated that the mechanical properties of the conductive GelMA–collagen–AgNW blended hydrogels improved. Biocompatibility analysis confirmed that the human umbilical vein endothelial cells (HUVECs) encapsulated within the three-dimensional (3D), conductive blended hydrogels were highly viable. Furthermore, we confirmed that the molecule in the conductive blended hydrogel was released by electrical stimuli-mediated structural deformation. Therefore, this conductive GelMA–collagen–AgNW blended hydrogel could be potentially used as a smart actuator for drug delivery applications.


Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2950
Author(s):  
Hongwei Song ◽  
Xinle Li

The most active research area is nanotechnology in cementitious composites, which has a wide range of applications and has achieved popularity over the last three decades. Nanoparticles (NPs) have emerged as possible materials to be used in the field of civil engineering. Previous research has concentrated on evaluating the effect of different NPs in cementitious materials to alter material characteristics. In order to provide a broad understanding of how nanomaterials (NMs) can be used, this paper critically evaluates previous research on the influence of rheology, mechanical properties, durability, 3D printing, and microstructural performance on cementitious materials. The flow properties of fresh cementitious composites can be measured using rheology and slump. Mechanical properties such as compressive, flexural, and split tensile strength reveal hardened properties. The necessary tests for determining a NM’s durability in concrete are shrinkage, pore structure and porosity, and permeability. The advent of modern 3D printing technologies is suitable for structural printing, such as contour crafting and binder jetting. Three-dimensional (3D) printing has opened up new avenues for the building and construction industry to become more digital. Regardless of the material science, a range of problems must be tackled, including developing smart cementitious composites suitable for 3D structural printing. According to the scanning electron microscopy results, the addition of NMs to cementitious materials results in a denser and improved microstructure with more hydration products. This paper provides valuable information and details about the rheology, mechanical properties, durability, 3D printing, and microstructural performance of cementitious materials with NMs and encourages further research.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4164
Author(s):  
Elizabeth Diederichs ◽  
Maisyn Picard ◽  
Boon Peng Chang ◽  
Manjusri Misra ◽  
Amar Mohanty

Three-dimensional (3D) printing manufactures intricate computer aided designs without time and resource spent for mold creation. The rapid growth of this industry has led to its extensive use in the automotive, biomedical, and electrical industries. In this work, biobased poly(trimethylene terephthalate) (PTT) blends were combined with pyrolyzed biomass to create sustainable and novel printing materials. The Miscanthus biocarbon (BC), generated from pyrolysis at 650 °C, was combined with an optimized PTT blend at 5 and 10 wt % to generate filaments for extrusion 3D printing. Samples were printed and analyzed according to their thermal, mechanical, and morphological properties. Although there were no significant differences seen in the mechanical properties between the two BC composites, the optimal quantity of BC was 5 wt % based upon dimensional stability, ease of printing, and surface finish. These printable materials show great promise for implementation into customizable, non-structural components in the electrical and automotive industries.


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